OBJECTIVES: The core pathology of osteoporosis lies in bone resorption exceeding bone formation; thus, promoting osteogenesis is a key therapeutic strategy. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) forms the biological basis of bone formation. Astragaloside IV (A-IV), a major active component of Astragalus membranaceus, is known to enhance osteogenesis, but its precise molecular mechanisms remain unclear. This study aims to investigate the effects of A-IV on the proliferation and osteogenic differentiation of BMSCs from osteoporotic rats and to elucidate its molecular mechanism through the regulation of microRNA-21 (miR-21) and Notch2 expression. METHODS: After 1 week of adaptive feeding, mature female SD rats were randomly divided into a sham-operated (Sham) group (n=4) and an ovariectomized (OVX) group (n=8) to establish an osteoporosis model. Twelve weeks after surgery, BMSCs were isolated from femoral bone marrow and cultured. Cells were divided into a S-BMSCs group (from Sham), an O-BMSCs group (from OVX), and an A-BMSCs group (from OVX-derived BMSCs treated with A-IV). S-BMSCs and O-BMSCs were induced for osteogenic differentiation using osteogenic induction medium, whereas A-BMSCs were treated with A-IV before induction. Flow cytometry was used to identify mesenchymal stem cell surface markers (CD29) and hematopoietic stem cell marker (CD34) to confirm BMSC characteristics. Cell proliferation was assessed using the methyl thiazolyl tetrazolium (MTT) assay. Alizarin red staining was performed to quantify calcium nodule formation, and alkaline phosphatase (ALP) activity assays were used to evaluate osteogenic differentiation. Real-time reverse transcription PCR (real-time RT-PCR) was used to detect changes in osteogenic-related genes, runt-related transcription factor 2 (Runx2) and osteopontin (OPN), as well as miR-21 expression. Western blotting was performed to assess Runx2, OPN, and Notch2 protein expression. RESULTS: Flow cytometry confirmed that O-BMSCs retained the phenotypic characteristics of mesenchymal stem cells. A-IV significantly enhanced the proliferation of BMSCs from osteoporotic rats (P<0.05), increased ALP activity, and upregulated the mRNA and protein expression of Runx2 and OPN (P<0.05). Bioinformatic and experimental analyses demonstrated that miR-21 directly targeted Notch2. A-IV treatment increased miR-21 expression while suppressing Notch2 protein expression and inhibiting activation of the Notch signaling pathway (P<0.05). CONCLUSIONS Astragaloside IV promotes the osteogenic differentiation of BMSCs derived from osteoporotic rats by upregulating miR-21 expression and inhibiting the key Notch signaling protein Notch2, thereby relieving the Notch2-mediated suppression of osteogenesis.
Animals ; Triterpenes/pharmacology* ; Saponins/pharmacology* ; Osteogenesis/drug effects* ; MicroRNAs/metabolism* ; Rats, Sprague-Dawley ; Female ; Cell Differentiation/drug effects* ; Mesenchymal Stem Cells/drug effects* ; Signal Transduction/drug effects* ; Osteoporosis/pathology* ; Rats ; Cells, Cultured ; Receptor, Notch2/metabolism* ; Receptors, Notch/metabolism* ; Ovariectomy ; Cell Proliferation/drug effects*

OBJECTIVES: To propose a single repetition time (TR) quantitative magnetic susceptibility imaging method for the lumbar spine using bipolar readout gradient, and compare the quantitative magnetic susceptibility measurement using single TR and dual TR methods for the lumbar spine with different bone densities. METHODS: A translation correction method was proposed to correct spatial misalignment along the frequency encoding direction between positive and negative gradient readout images, and the phase difference between the images was eliminated using a phase correction method. The data of lumbar vertebrae L1-L5 were collected using single TR and dual TR methods from 6 normal individuals, 2 patients with osteopenia, and 2 patients with osteoporosis. The magnetic susceptibility map was reconstructed, the quantitative results of single TR before and after correction were compared with those of the dual TR method. RESULTS: The linear regression result of the lumbar spine magnetic susceptibility values obtained by the single TR method before calibration and the dual TR method is Y=0.64*X-11.61. The linear regression result of the lumbar spine magnetic susceptibility values corrected by the single TR method and the dual TR method is Y=1.03*X+0.25. The results of the corrected single TR method were highly consistent with those of the dual TR method, and the calibrated single TR method could effectively distinguish osteopenia and osteoporosis patients from normal individuals. CONCLUSIONS The calibrated single TR bipolar readout gradient method can generate artifact-free lumbar spine quantitative magnetic susceptibility distribution maps and reduce data acquisition time by 50%.
Humans ; Lumbar Vertebrae/pathology* ; Magnetic Resonance Imaging/methods* ; Female ; Middle Aged ; Male ; Osteoporosis/diagnosis* ; Adult ; Bone Density ; Aged ; Bone Diseases, Metabolic/diagnosis*

Aging is typically associated with decreased musculoskeletal function, leading to reduced mobility and increased frailty. As a hallmark of aging, cellular senescence plays a crucial role in various age-related musculoskeletal diseases, including osteoporosis, osteoarthritis, intervertebral disc degeneration, and sarcopenia. The detrimental effects of senescence are primarily due to impaired regenerative capacity of stem cells and the pro-inflammatory environment created by accumulated senescent cells. The secreted senescence-associated secretory phenotype (SASP) can induce senescence in neighboring cells, further amplifying senescent signals. Although the removal of senescent cells and the suppression of SASP factors have shown promise in alleviating disease progression and restoring musculoskeletal health in mouse models, clinical trials have yet to demonstrate significant efficacy. This review summarizes the mechanisms of cellular senescence in age-related musculoskeletal diseases and discusses potential therapeutic strategies targeting cellular senescence.
Humans ; Cellular Senescence/physiology* ; Musculoskeletal Diseases/pathology* ; Aging/pathology* ; Animals ; Senescence-Associated Secretory Phenotype/physiology* ; Sarcopenia ; Osteoporosis

OBJECTIVE: To explore relationship between bone marrow edema(BME) and osteoporosis in patients with severe knee osteoarthritis. METHODS: Unmatched case-control study was conducted. Totally 160 patients with severe knee osteoarthritis who had undergone knee magnetic resonance imaging (MRI) and bone mineral density examination (BMD) from January 2020 to March 2021 were included. Eighty patients complicated with BME were included in BME group, and 80 patients without BME were selected as NBME group. In BME group, there were 12 males and 68 females, aged from 51 to 80 years old with an average of(66.58±8.10) years old;the courses of disease ranged from 5 to 40 months with an average of (15.61±9.25) months;body mass index(BMI) ranged from 21.81 to 34.70 with an average of (27.79±3.00) kg·m^-2;25 patients classified to grade Ⅲ and 55 patients grade Ⅳ according to Kellgren- Lawrence(K-L). In NBME group, there were 15 males and 65 females, aged from 50 to 80 years old with an average of(67.82±8.05) years old;the course of disease ranged from 6 to 37 months with an average of(15.75±8.18) months;BMI ranged from 21.39 to 34.46 with an average of (28.26±3.13) kg·m^-2;25 patients were K-L Ⅲ and 55 patients with K-L Ⅳ. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score(WORMS). Osteoporosis was diagnosed and BMD was evaluated by DXA T value. To explore the relationship between bone marrow edema and osteoporosis by comparing prevalence rate of osteoporosis between two groups, and to further explore relationship between BME and BMD by Spearman correlation analysis of BME WORMS score and DXA T value in BME group. RESULTS: The complete case data were obtained on the first diagnosis, and there was no significant difference in sex, age, courses of disease and BMI between two groups (P>0.05). The proportion of K-L Ⅳ in BME group was significantly higher than that in NBME (P<0.05). The prevalence rate of osteoporosis in BME group was significantly higher than in NBME group with the same K-L grade (P<0.001), and there was a strong negative correlation between BME WORMS score and DXA BMD T value (r=-0.812, |r|=0.812 >0.8, P<0.001). CONCLUSION Osteoporosis is one of the risk factors of bone marrow edema in patients with severe knee osteoarthritis, and the lower the bone mineral density is, the easier it is to be complicated with bone marrow edema.
Male ; Female ; Humans ; Osteoarthritis, Knee/diagnostic imaging* ; Bone Marrow/pathology* ; Case-Control Studies ; Bone Marrow Diseases/etiology* ; Osteoporosis/complications* ; Edema/etiology* ; Magnetic Resonance Imaging/methods*

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, 53 mL/min/1.73 m²). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.
Acidosis, Renal Tubular ; Adult ; Biopsy ; Blood Urea Nitrogen ; Bone Density ; Creatinine ; Drug-Related Side Effects and Adverse Reactions ; Fanconi Syndrome ; Female ; Glomerular Filtration Rate ; Glycosuria, Renal ; Humans ; Hypophosphatemia, Familial ; Middle Aged ; Molecular Biology ; Osteoporosis ; Parathyroid Hormone ; Pathology ; Proteinuria ; Vitamin D

STUDY DESIGN: Single-center, retrospective case series. PURPOSE: To investigate the effectiveness of posterior vertebrectomy and circumferential fusion in patients with advanced Kümmell disease with neurologic deficit. OVERVIEW OF LITERATURE: Various surgical options exist for the treatment of Kümmell disease, and determination of the appropriate treatment is based on the clinical and radiologic status of the patient. However, surgical intervention is required for patients with advanced Kümmell disease accompanied by neurologic deficit. METHODS: We retrospectively analyzed 22 neurologically compromised patients with advanced Kümmell disease who were treated surgically at Ewha Womans Hospital between January 2011 and January 2014. The surgical approach used by us was a posterior vertebrectomy with mesh cage insertion and segmental cement-augmented pedicle screw fixation. The tissue from the corpectomy was histopathologically examined. Anterior vertebral height, kyphotic angle, visual analog scale (VAS) score, and the Frankel classification were used to evaluate the efficacy of the procedure. RESULTS: The mean follow-up period was 26 months (range, 13–40 months). VAS score, anterior vertebral height, kyphotic angle, and neurologic state were significantly improved immediately postoperatively and at the last follow-up compared with preoperatively (p<0.05). Most patients exhibited intravertebral clefts on imaging, and postoperative pathology revealed bone necrosis. CONCLUSIONS: Posterior vertebrectomy with mesh cage insertion and segmental cement-augmented pedicle screw fixation is an effective approach for treating patients with advanced Kümmell disease with neurologic deficit.
Classification ; Female ; Follow-Up Studies ; Humans ; Kyphosis ; Necrosis ; Neurologic Manifestations* ; Osteoporosis ; Pathology ; Pedicle Screws ; Retrospective Studies ; Visual Analog Scale

OBJECTIVE: To map the progression of osteoporosis following spinal cord injury in mice in specific areas and analyze changes in parathyroid hormone (PTH) and ion levels which could be responsible for overall bone loss. SUMMARY OF BACKGROUND DATA: Spinal cord injury rapidly induces severe bone loss compared to other conditions, yet the cause of this bone loss has not been identified. Studies suggest the bone loss after injury is not solely due to disuse. METHODS: To quantify bone loss we weighed individual bones and measured bone mineral density using dual energy X-ray absorptiometry at acute (1 week) and chronic (4 week) time points following a T9 contusion. An ELISA was used to measure blood PTH levels at 1 and 4 weeks after injury. Calcium and phosphate levels were also analyzed at 4 weeks following injury at the University of Miami pathology core. RESULTS: We observed a significant decrease in bone mineral density in hind limbs after an acute injury, and found this bone loss to progress over time. Furthermore, following chronic injury a decrease in bone mineral density is also observed in bones above the level of injury and in the total bone mineral density. We observed a significant decrease in parathyroid hormone levels in injured mice at the chronic time point, but not at the acute time point which suggests this could be involved in the global bone loss following injury. We also observed a significant increase in serum calcium levels following injury which could account for the imbalance of PTH levels.
Absorptiometry, Photon ; Animals ; Bone Density ; Calcium ; Contusions ; Enzyme-Linked Immunosorbent Assay ; Extremities ; Mice* ; Osteoporosis ; Parathyroid Hormone ; Pathology ; Spinal Cord Injuries* ; Spinal Cord*

Osteoporosis is a bone pathology leading to increased fracture risk and challenging the quality of life. The aim of this study was to evaluate the effect of an anthraquinone glycoside, aloin, on osteogenic induction of MC3T3-E1 cells. Aloin increased alkaline phosphatase (ALP) activity, an early differentiation marker of osteoblasts. Aloin also increased the ALP activity in adult human adipose-derived stem cells (hADSC), indicating that the action of aloin was not cell-type specific. Alizarin red S staining revealed a significant amount of calcium deposition in cells treated with aloin. Aloin enhanced the expression of osteoblast differentiation genes, Bmp-2, Runx2 and collagen 1a, in a dose-dependent manner. Western blot analysis revealed that noggin and inhibitors of p38 MAPK and SAPK/JNK signals attenuated aloin-promoted expressions of Bmp-2 and Runx2 proteins. siRNA mediated blocking of Wnt-5a signaling pathway also annulled the influence of aloin, indicating Wnt-5a dependent activity. Inhibition of the different signal pathways abrogated the influence of aloin on ALP activity, confirming that aloin induced MC3T3-E1 cells into osteoblasts through MAPK mediated Wnt and Bmp signaling pathway.
Adult ; Alkaline Phosphatase ; Blotting, Western ; Calcium ; Collagen ; Core Binding Factor Alpha 1 Subunit ; Humans ; Osteoblasts ; Osteoporosis ; p38 Mitogen-Activated Protein Kinases ; Pathology ; Quality of Life ; RNA, Small Interfering ; Signal Transduction ; Stem Cells

STUDY DESIGN: Retrospective observational study. PURPOSE: To identify the role of percutaneous vertebral biopsy in histopathological diagnosis of vertebral compression fractures and to identify the frequency of unexpected malignancy in vertebral compression fractures. OVERVIEW OF LITERATURE: Vertebral compression fractures are common in the Indian population. Magnetic resonance imaging and nuclear imaging have some limitations in the diagnosis of definitive pathology of vertebral compression fractures. Therefore, histological confirmation is necessary for definitive diagnosis and to plan appropriate management for patient. METHODS: A retrospective observational study was conducted involving 84 patients who underwent percutaneous vertebral biopsy between 2010 and 2014. We performed C-arm guided percutaneous transpedicular core vertebral biopsy of vertebral compression fractures under combination of local anesthesia and intravenous conscious sedation. RESULTS: Sufficient biopsy material was obtained in 79 of the 84 cases. In the other five cases, biopsy material was not sufficient for reporting. Out of the 79 cases, osteoporotic pathology was detected in 69 patients, malignancy was detected in 8 patients and no pathology was found in 2 patients. Two patients with distant metastases to vertebra were identified. Primary spinal malignancy was detected in 6 patients (1 unsuspected plasmacytoma, 5 diagnosed malignancy preoperatively). So, the frequency of unsuspected malignancy of this study was 1.19% (1/84). None of the patients had any complications. CONCLUSIONS: C-arm guided percutaneous transpedicular vertebral biopsy is useful in obtaining definitive histopathological diagnosis of vertebral compression fractures, especially in differentiating malignant and non-malignant vertebral compression fractures and helping plan appropriate management of patients. The rate of unexpected malignancy in vertebral compression fracture was 1.19%.
Anesthesia, Local ; Biopsy* ; Biopsy, Needle ; Conscious Sedation ; Diagnosis* ; Fractures, Compression* ; Humans ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Neoplasms, Second Primary ; Observational Study ; Osteoporosis ; Pathology* ; Plasmacytoma ; Retrospective Studies ; Spine

OBJECTIVETo evaluate the therapeutic effects of conservative treatment of refracture in cemented vertebrae after percutaneous vertebroplasty for osteoporotic vertebral compression fractures in elderly patients.

METHODSBetween January, 2012 and August, 2014, a total of 324 elderly patients (381 vertebrae) received percutaneous vertebroplasty for osteoporotic vertebral compression fractures. Of these patients, 12 patients (14 vertebrae) complained of recurrence of back pain and were confirmed to have refracture in the cemented vertebrae by imaging examination. Seven of these 12 patients (9 vertebrae), who were all female with an average refracture time of 8±6.7 weeks (range 2-20 weeks), received conservative treatments with analgesics, osteoporosis medication, bracing and physical therapy, and their visual analogue scale (VAS) scores and Oswestry disability index (ODI) at 7 days and 1, 3 and 12 months after the treatment were measured.

RESULTSThe 7 patients were followed up for 21.3±11.2 months (range 13-29 months) after conservative treatments. Their VAS score and ODI decreased significantly over time after the treatment (P<0.05) and showed significant differences between the measurements at 7 days, 1 and 3 months (P<0.05) but not between 3 and 12 months (P>0.05). The average VAS score and ODI before treatments were 8.3±0.8 and (88.3±3.2)%, 3.1±1.2 and (56.3±7.7)% at 1 month, and 0.8±0.7 and (5.9±2.8)% at 3 months during the follow-up, respectively.No such complications as phlebothrombosis of the leg, decubitus, or hypostatic pneumonia occurred in these cases.

CONCLUSIONThough with a relatively low incidence rate, refracture in the cemented vertebrae is one of the important causes of recurrence of back pain following percutaneous vertebroplasty. Conservative treatment is effective in relieving pain and improving the spine function in such cases without obvious complications.

Aged ; Analgesics ; therapeutic use ; Back Pain ; therapy ; Bone Cements ; Female ; Fractures, Compression ; surgery ; therapy ; Humans ; Osteoporosis ; surgery ; therapy ; Pain Management ; Pain Measurement ; Recurrence ; Spinal Fractures ; surgery ; therapy ; Spine ; pathology ; Treatment Outcome ; Vertebroplasty