Insights into the mechanical microenvironment within the cartilaginous endplate: An emerging role in maintaining disc homeostasis and normal function.

Biomechanical factors are strongly linked with the emergence and development of intervertebral disc degeneration (IVDD). The intervertebral disc (IVD), as a unique enclosed biomechanical structure, exhibits distinct mechanical properties within its substructures. Damage to the mechanical performance of any substructure can disrupt the overall mechanical function of the IVD. Endplate degeneration serves as a significant precursor to IVDD. The endplate (EP) structure, especially the cartilaginous endplate (CEP), serves as a conduit for nutrient and metabolite transport in the IVD. It is inevitably influenced by its nutritional environment, mechanical loading, cytokines and extracellular components. Currently, reports on strategies targeting the CEP for the prevention and treatment of IVDD are scarce. This is due to two primary reasons: first, limited knowledge of the biomechanical microenvironment surrounding the degenerated CEP cells; and second, innovative biological treatment strategies, such as implanting active cells (disc or mesenchymal stem cells) or modulating natural cell activity through the addition of therapeutic factors or genes to treat IVDD often overlook a critical aspect-the restoration of the nutrient supply function and mechanical microenvironment of the endplate. Therefore, restoring the healthy structure of the CEP and maintaining a stable mechanical microenvironment within the EP are crucial for the prevention of IVDD and the repair of degenerated IVDs. We present a comprehensive literature review on the mechanical microenvironment characteristics of cartilage endplates and their associated mechanical signaling pathways. Our aim is to provide valuable insights into the development and implementation of strategies to prevent IVDD by delaying or reversing CEP degeneration.

Noncontact elasticity measurement of hydrogels in a culture dish using reverberant optical coherence elastography.

Estimating the elasticity of hydrogel phantoms in a cell culture plane is important for understanding the cell behavior in response to various types of mechanical stimuli. Hence, a noncontact tool for measuring the elastic properties of hydrogel phantoms in such three-dimensional cell cultures is required. A well-known method to determine the mechanical properties of hydrogels is the transient wave method. However, due to the multiple reflections of waves from the boundaries, a bigger cell culture plane or multiple directional filters may be required. In this study, we utilized reverberant shear wave elastography, which is based on the autocorrelation principle, to evaluate the shear wave speed in hydrogel samples within a culture dish. Numerical simulations were performed first to confirm the validity of the reverberant elastography method. Subsequently, we used this method to measure the wave speeds in hydrogel phantoms with different concentrations. Shear rheology tests were also performed, and their results were found to be in good agreement with the measured shear wave speeds. The proposed method could be useful for measuring the elasticity of tissues in tissue engineering applications in an inexpensive and noncontact manner.

Effect of polydimethylsiloxane surface morphology on osteogenic differentiation of mesenchymal stem cells through SIRT1 signalling pathway.

Constructing surface topography with a certain roughness is a widely used, non-toxic, cost-effective and effective method for improving the microenvironment of cells, promoting the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs), and promoting the osseointegration of grafts and further improving their biocompatibility under clinical environmental conditions. SIRT1 plays an important regulatory role in the osteogenic differentiation of bone marrow-derived MSCs (BM-MSCs). However, it remains unknown whether SIRT1 plays an important regulatory role in the osteogenic differentiation of BM-MSCs with regard to surface morphology. Polydimethylsiloxane (PDMS) with different surface morphologies were prepared using different grits of sandpaper. The value for BMSCs added on different surfaces was detected by cell proliferation assays. RT-qPCR and Western blotting were performed to detect SIRT1 activation and osteogenic differentiation of MSCs. Osteogenesis of MSCs was detected by alkaline phosphatase (ALP) and alizarin red S staining. SIRT1 inhibition experiments were performed to investigate the role of SIRT1 in the osteogenic differentiation of MSCs induced by surface morphology. We found that BM-MSCs have better value and osteogenic differentiation ability on a surface with roughness of PDMS-1000M. SIRT1 showed higher gene and protein expression on a PDMS-1000M surface with a roughness of 13.741 ± 1.388 µm. The promotion of the osteogenic differentiation of MSCs on the PDMS-1000M surface was significantly decreased after inhibiting SIRT1 expression. Our study demonstrated that a surface morphology with certain roughness can activate the SIRT1 pathway of MSCs and promote the osteogenic differentiation of BMSCs via the SIRT1 pathway.

Betulinic Acid Attenuates Osteoarthritis via Limiting NLRP3 Inflammasome Activation to Decrease Interleukin-1ß Maturation and Secretion.

Introduction: Osteoarthritis (OA) is the most common degenerative joint disorder. Prior studies revealed that activation of NLRP3 inflammasome could promote the activation and secretion of interleukin-1ß (IL-1ß), which has an adverse effect on the progression of OA. Betulinic acid (BA) is a compound extract of birch, whether it can protect against OA and the mechanisms involved are still unknown. Materials and Methods: In vivo experiments, using gait analysis, ELISA, micro-CT, and scanning electron microscopy (SEM), histological staining, immunohistological (IHC) and immunofluorescence (IF) staining, and atomic force microscopy (AFM) to assess OA progression after intraperitoneal injection of 5 and 15 mg/kg BA in an OA mouse model. In vitro experiments, caspase-1, IL-1ß, and the N-terminal fragment of gasdermin D (GSDMD-NT) were measured in bone marrow-derived macrophages (BMDMs) by using ELISA, western blot, and immunofluorescence staining. Results: We demonstrated that OA progression can be postponed with intraperitoneal injection of 5 and 15 mg/kg BA in an OA mouse model. Specifically, BA postponed DMM-induced cartilage deterioration, alleviated subchondral bone sclerosis, and relieved synovial inflammation. In vitro studies, the activated NLRP3 inflammasome produces mature IL-1ß by facilitating the cleavage of pro-IL-1ß, and BA could inhibit the activation of NLRP3 inflammasome in BMDMs. Conclusions: Taken together, our analyses revealed that BA attenuates OA via limiting NLRP3 inflammasome activation to decrease the IL-1ß maturation and secretion.

Recurrence of Local Kyphosis After Percutaneous Kyphoplasty: The Neglected Injury of the Disc-Endplate Complex.

Background: Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures. Patients and Methods: A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors. Results: During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81±8.60° postoperatively to 25.13±8.91° at the final follow-up which showed a statistically significant difference (p<0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values (p<0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc-endplate complex injury (OR=17.46, p=0.003); local kyphosis angle correction (OR=1.84, p<0.001); and vertebral height restoration (OR=1.15, p=0.003) were risk factors for re-kyphosis. Conclusion: Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc-endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.

Establishment of Ferroptosis-Related Key Gene Signature and Its Validation in Compression-Induced Intervertebral Disc Degeneration Rats.

Cell death and functional loss of nucleus pulposus cell play essential roles in intervertebral disc degeneration (IDD). Ferroptosis is a newly identified cell death type, and its role in IDD is still under investigation. Identifying the key genes of ferroptosis in IDD helps to identify the therapeutic targets of IDD. In this study, we downloaded the human IDD mRNA microarray data from the Gene Expression Omnibus and ferroptosis genes from FerrDb, then performed a series of analyses using strict bioinformatics algorithms. In general, we obtained 40 ferroptosis-related differential expression genes (FerrDEGs) and identified six ferroptosis key gene signatures, namely, ATF3, EIF2S1, AR, NQO1, TXNIP, and AKR1C3. In addition, enrichment analysis of the FerrDEGs was conducted, the protein-protein interaction network was constructed, the correlations between ferroptosis key genes and immune infiltrating cells were analyzed, and the lncRNA-miRNA-mRNA ceRNA network was constructed. In particular, ATF3 and EIF2S1 showed the strongest correlation with immune cell function, which might lead to the development of IDD. Finally, the expressions of ferroptosis key genes were verified in the rat compression-induced IDD. In conclusion, this preliminary study analyzed and verified the mechanism of ferroptosis in IDD, laid a foundation for the follow-up study of the mechanism of ferroptosis in IDD, and provided new targets for preventing and delaying IDD.

Bilateral percutaneous kyphoplasty achieves more satisfactory outcomes compared to unilateral percutaneous kyphoplasty in osteoporotic vertebral compression fractures: A comprehensive comparative study.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) are the most common complication of osteoporosis, a worldwide disease that disturbs the elderly. OBJECTIVE: The purpose of the study was to comprehensively compare the clinical efficacy of unilateral percutaneous kyphoplasty (UPKP) and bilateral percutaneous kyphoplasty (BPKP) when treating OVCFs and evaluate their ability to maintain the outcomes in a 2-year follow-up. METHODS: From January 2015 to December 2016 a total of 79 patients with OVCFs were included in the study. They were divided into UPKP group and BPKP group. Subsequently, perioperative data, radiological outcomes, clinical outcomes, and complications were compared between two groups. The follow-up consultation was 3 months, 1 year, and 2 years after the operation. RESULTS: 37 of patients (14 males, 23 females) were allocated to the UPKP group and 42 patients (13 males, 29 females) were treated with BPKP. The duration of operation and injected cement volume were significantly higher in the BPKP group than those of the UPKP group. BPKP achieved significantly higher improvement in middle height and volume of the fractured vertebral body than UPKP did. There were significantly higher losses of anterior, middle height and volume of the fractured vertebral body in the UPKP group at 2-year follow-up than in the BPKP group. At the final follow-up, Oswestry Disability Index (ODI) of BPKP group was lower than that of UPKP group. CONCLUSION: Both UPKP and BPKP achieve satisfactory radiological and clinical outcomes when treating OVCFs. However, in a 2-year follow-up, BPKP maintains vertebral height restoration, volume of vertebral body, and ODI better than UPKP do.

A Device for Isolation of Selected Single Adherent Cells.

In recent years, extensive research has been focused on the field of single cell analysis. The isolation of single cells is the first step in this type of research. However, the techniques used for direct isolation and acquisition of single adherent cells are limited. Here, we present a method of obtaining selected single adherent cells using a separation device. Compared with other single cell isolation methods, this method has the advantages of simple operation, low cost, minimal cell damage, and preservation of cell morphology. Our methodology is, therefore, suitable for the collection of selected single adherent cells.

Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics.

BACKGROUND: Conservative treatment is the recommended first-line treatment for degenerative disc diseases. Traction therapy has historically been one of the most common clinical methods to address this, but the clinical effect remains controversial. METHODS: Forty-two six-month-old male Sprague-Dawley rats were randomly divided into six groups: the model group (Group A, four coccyx vertebrae (Co7-Co10) were fixed with customized external fixators, and the vertebral disc degeneration model was constructed by axial compression of the target segment Co8 - Co9 for 4 weeks), the experimental control group (Group B, after successful modeling, the external fixation device was removed and self-rehabilitation was performed) and four intervention groups (Groups C to F): Groups C and E: Co8 - Co9 vertebrae compressed for 4 weeks followed by two or 4 weeks of high tension traction (HTT), respectively, and Groups D and F: vertebrae compressed for 4 weeks followed by two or 4 weeks of low-tension traction (LTT), respectively. Imaging tests (X-ray and MRI) were performed to assess disc height and T2 signal intensity at each time point. After the experiment, the animals were euthanized, and the caudal vertebrae were collected for analysis of intervertebral disc histopathology, proteoglycan content, and micronanostructure of the annulus fibrosus, nucleus pulposus and bony endplate. RESULTS: Signs of tissue regeneration were apparent in all four intervention groups. After two to 4 weeks of intervention (HTT and LTT), the morphology of pores in the bony endplate, their number, and diameter had recovered significantly compared with those in Group A. The LTT group was superior to the HTT group, and the 4w in situ group was significantly superior to the 2w group. Meanwhile, the histological scores of discs, the mean fibril diameter and modulus of annulus fibrosus were significantly improved compared with the control groups, and the LTT group was superior to HTT group. CONCLUSIONS: Low-tension traction better promotes active reconstruction of bony endplates and improves the elastic modulus and micro/nanostructure of the disc. Thus, it further promotes the regeneration and repair of intervertebral discs.

Ligamentous injury-induced ankle instability causing posttraumatic osteoarthritis in a mouse model.

BACKGROUND: This study aims to explore the relationship between surgically-induced ankle instability and posttraumatic osteoarthritis (PTOA) in a mouse model, and to provide reference for clinical practice. RESULTS: Ligamentectomy was performed on 24 eight-week-old male C57BL/6 J mice, which were divided into three groups. Both the anterior talofibular ligament (ATFL) and the calcaneofibular ligament (CFL) were severed in the CFL + ATFL group, while only the CFL was removed in the CFL group. The SHAM group was set as the blank control group. A wheel-running device was used to accelerate the development of ankle osteoarthritis (OA). Balance measurement, footprint analysis, and histological analysis were used to assess the degree of ankle instability and OA. According to the balance test results, the CFL + ATFL group demonstrated the highest number of slips and the longest crossing beam time at 8 weeks postoperatively. The results of gait analysis exhibited that the CFL + ATFL group had the most significant asymmetry in stride length, stance length, and foot base width compared to the CFL and SHAM groups. The OARSI score of the CFL + ATFL group (16.7 ± 2.18) was also much higher than those of the CFL group (5.1 ± 0.96) and the SHAM group (1.6 ± 1.14). CONCLUSION: Based on the mouse model, the findings indicate that severe ankle instability has nearly three times the chance to develop into ankle OA compared to moderate ankle instability.

Corrigendum to "Salvianolic Acid B Protects Intervertebral Discs from Oxidative Stress-Induced Degeneration via Activation of the JAK2/STAT3 Signaling Pathway".

[This corrects the article DOI: 10.1155/2021/6672978.].

Identification of Prognostic lncRNA Related to the Immune Microenvironment of Soft Tissue Sarcoma.

BACKGROUND: Soft tissue sarcoma is a malignant tumor with high degree of malignancy and poor prognosis, originating from mesenchymal tissue. Long noncoding RNAs (lncRNAs) are involved in various biological and pathological processes in the body. They perform preprocessing, splicing, transport, degradation, and translation of mRNA to achieve posttranscriptional level regulation, resulting in the occurrence, invasion, and metastasis of tumors. Therefore, they are highly relevant with regard to early diagnoses and as prognostic indicators. OBJECTIVE: The objective of the present study was to identify immune microenvironment-related lncRNAs that can be used to predict soft tissue sarcomas. METHODS: Clinical data and follow-up data were obtained from the cBioPortal database, and RNA sequencing data used for the model structure can be accessed from The Cancer Genome Atlas (TCGA) database. LncRNAs were screened by differential expression analysis and coexpression analysis. The Cox regression model and Kaplan-Meier analysis were used to study the association between lncRNAs and soft tissue sarcoma prognosis in the immune microenvironment. Unsupervised cluster analysis was then completed to discover the impact of screening lncRNAs on disease. We constructed an mRNA-lncRNA network by Cytoscape software. Finally, qRT-PCR was used to verify the difference in the expression of the lncRNAs in normal cells and sarcoma cells. RESULTS: Unsupervised cluster analysis revealed that the 210 lncRNAs screened showed strong correlation with the tumor immune microenvironment. Two signatures containing seven and five lncRNAs related to the tumor microenvironment were constructed and used to predict overall survival (OS) and disease-free survival (DFS). The Kaplan-Meier (K-M) survival curve showed that the prognoses of patients in the high-risk and low-risk groups differed significantly, and the prognosis associated with the low-risk group was better than that associated with the high-risk group. Two nomograms with predictive capabilities were established. qRT-PCR results showed that the expression of AC108134.3 and AL031717.1 was significantly different in normal and sarcoma cells. CONCLUSION: In summary, the experimental results showed that lncrnA associated with immune microenvironment was related to tumor, which may provide a new idea for immunotherapy of STS.

Similarity and difference between aging and puncture-induced intervertebral disc degeneration.

The purpose of our study was to investigate the changes in micromorphology and mechanical properties of intervertebral discs degeneration induced by aging and puncture. Normal group (NG), 2 weeks post-puncture degeneration group (PDG) and aging degeneration group (ADG) each included 10 rats. Plain film, magnetic resonance imaging, and histological testing were utilized to assess intervertebral disc degeneration. Atomic force microscope was utilized to analyze the microstructure and elastic modulus of the intervertebral disc, while immunohistochemistry was employed to assess alterations in the cell matrix using collagen I, collagen II, matrix metalloproteinase-3 (MMP-3), and tumour necrosis factor-α (TNF-α). The results showed that the disc height ratio between PDG and ADG decreased. In the PDG and ADG group, histological scores both increased, the gray value of the T2 signal decreased, the proportion of MMP-3 and TNF-positive cells in intervertebral disc tissues was higher (p < 0.05) and the IOD values of COL-2 lower in intervertebral disc tissues (p < 0.05). The elastic modulus of PDG and ADG annulus fibers (AF) increased compared to the NG (p < 0.05); when compared to PDG, the elastic modulus of ADG AF decreased (p < 0.05). The elastic modulus of PDG and ADG collagen increased in the nucleus pulposus (NP, p < 0.05); ADG had a greater AF diameter than NG and PDG (p < 0.05). The results indicated that ADG fiber diameter thickens, and chronic inflammation indicators rise; PDG suffers from severe extracellular matrix loss. The degeneration of the ADG and PDG intervertebral discs is different. The results provide foundation for clinical research.

Stiffness of the extracellular matrix affects apoptosis of nucleus pulposus cells by regulating the cytoskeleton and activating the TRPV2 channel protein.

It is known that nucleus pulposus cells (NPs) play an important role in intervertebral disc degeneration (IVDD), and a previous study indicated that the stiffness of NP tissue changes during the degeneration process. However, the mechanism underlying the cellular response to ECM stiffness is still unclear. To analyze the effects of extracellular matrix (ECM) with different degrees of stiffness on NPs, we prepared polyacrylamide (PA) gels with different elastic moduli, and cells grown under different stiffness conditions were obtained and analyzed. The results showed that the spreading morphology of NPs changed significantly under increased ECM elastic modulus conditions and that TRPV2 and the PI3K / AKT signaling pathway were activated by stiffer ECM. At the same time, mitochondria released cytochrome c (Cyt c) and activated caspase proteins to promote the apoptosis of NPs. After TRPV2 was specifically knocked out, the activation of the PI3K / AKT signaling pathway decreased, and the release of Cyt c and NP apoptosis were reduced. These results indicate that TRPV2 is closely linked to the detection of extracellular mechanical signals, and that conversion of mechanical and biological signals plays an important role in regulating the biological behavior of cells. This study offers a new perspective on the cellular and biochemical events underlying IVDD which could result in novel treatments.

Salvianolic Acid B Protects Intervertebral Discs from Oxidative Stress-Induced Degeneration via Activation of the JAK2/STAT3 Signaling Pathway.

OBJECTIVE: To evaluate the influence of salvianolic acid B (SAB), an antioxidant derived from Danshen, on intervertebral disc degeneration (IDD) and its possible molecular mechanisms. METHODS: Sixty adult rats were randomly grouped (control, IDD, and SAB IDD groups). IDD was induced using needle puncture. The rats received daily administration of SAB (20 mg/kg) in the SAB IDD group while the other two groups received only distilled water. The extent of IDD was evaluated using MRI after 3 and 6 weeks and histology after 6 weeks. Oxidative stress was assessed using the ELISA method. In in vitro experiments, nucleus pulposus cells (NPCs) were treated with H2O2 (100 µM) or SAB+H2O2, and levels of oxidative stress were measured. Cell apoptosis was assessed by flow cytometry, expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins. Cell proliferation rate was assessed by EdU analysis. Pathway involvement was determined by Western blotting while the influence of the pathway on NPCs was explored using the pathway inhibitor AG490. RESULTS: The data demonstrate that SAB attenuated injury-induced IDD and oxidative stress, caused by activation of the JAK2/STAT3 signaling pathway in vivo. Oxidative stress induced by H2O2 was reversed by SAB in vitro. SAB reduced the increased cell apoptosis, cleaved caspase-3 expression, and caspase-3 activity induced by H2O2. Reduced cell proliferation and decreased Bcl-2/Bax ratio induced by H2O2 were rescued by SAB. Additionally, the JAK2/STAT3 pathway was activated by SAB, while AG490 counteracted this effect. CONCLUSION: The results suggest that SAB protects intervertebral discs from oxidative stress-induced degeneration by enhancing proliferation and attenuating apoptosis via activation of the JAK2/STAT3 signaling pathway.

Assessment of viscoelasticity of ex vivo bovine cartilage using Rayleigh wave method in the near-source and far-field region.

Cartilage viscoelasticity changes as cartilage degenerates. Hence, a cartilage viscoelasticity measurement could be an alternative to traditional imaging methods for osteoarthritis diagnosis. In a previous study, we confirmed the feasibility of viscoelasticity measurement in ex vivo bovine cartilage using the Lamb wave method. However, the wave speed-frequency curve of Lamb wave is totally nonlinear and the cartilage thickness could significantly affect the Lamb wave speed, making wave speed measurements and viscoelasticity inversion difficult. The objective of this study was to measure the cartilage viscoelasticity using the Rayleigh wave method (RWM). Rayleigh wave speed in the ex vivo bovine cartilage was measured, and exists only in the near-source and far-field region. The estimated cartilage elasticity was 0.66 ± 0.05 and 0.59 ± 0.07 MPa for samples 1 and 2, respectively; the estimated cartilage viscosity was 24.2 ± 0.7 and 27.1 ± 1.8 Pa·s for samples 1 and 2, respectively. These results were found to be highly reproducible, validating the feasibility of viscoelasticity measurement in ex vivo cartilage using the RWM. Current method of cartilage viscoelasticity measurement might be translated into in vivo application.

Nano-elastic modulus of tendon measured directly in living mice.

The nano-biomechanical environment of the extracellular matrix is critical for cells to sense and respond to mechanical loading. However, to date, this important characteristic remains poorly understood in living tissue structures. This study reports the experimental measurement of the in vivo nano-elastic modulus of the tendon in a mouse tail model. The experiment was performed on the tail tendon of an 8-week-old C57BL/6 live mouse. Mechanical loading on tail tendons was regulated by changing both voltage and frequency of alternating current stimulation on the erector spinae. The nano-elastic modulus of the tail tendon was measured by atomic force microscope. The nano-elastic modulus showed significant variation (2.19-35.70 MPa) between different locations and up to 39% decrease under muscle contraction, suggesting a complicated biomechanical environment in which cells dwell. In addition, the nano-elastic modulus of the tail tendon measured in live mice was significantly lower than that measured in vitro, suggesting a disagreement of tissue mechanical properties in vivo and in vitro. This information is important for the designs of new extracellular biomaterial that can better mimic the biological environment, and improve clinical outcomes of musculoskeletal tissue degenerations and associated disorders.

Bone Mineral Density and Related Scores in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Parkinson's disease (PD) is the second most common degenerative neurologic disorder in older adults, and increasing attention has been paid to bone health in PD. Although several studies have shown that patients with PD have a lower bone mineral density (BMD) than do non-PD controls, there have been no systematic reviews in recent years. METHODS: PubMed, Medline, and Web of Science were used to search relevant studies up to May 2020. BMD, BMD T score, and BMD Z score of patients with and without PD were statistically analyzed. Meta-analysis was conducted using Review Manager version 5.3. RESULTS: This meta-analysis included 17 studies comprising 10,289 individuals. In the meta-analysis, adults with PD had lower total body, total hip, total radius, lumbar spine, total femur, femur neck, right-hand, and left-hand BMD than did non-PD controls. The T score of total body BMD, total hip BMD, total radius BMD, lumbar spine BMD, L1-L4 spine BMD, total femur BMD, and femur neck BMD in adults with PD were lower than those in non-PD controls. Futhermore, the Z score of total body BMD, total hip BMD, total radius BMD, lumbar spine BMD, L1-L4 spine BMD, and femur neck BMD was lower in adults with PD than in non-PD controls. CONCLUSIONS: Patients with PD had a lower BMD, BMD T score, and BMD Z score compared with non-PD controls. Therefore, clinicians should routinely monitor BMD of patients with PD to prevent falling and fragility fractures in older adults and optimize BMD before surgical treatment of severe spinal deformity caused by PD.