The complement factor H-related protein-5 (CFHR5) exacerbates pathological bone formation in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by excessive new bone formation. We previously reported that the complement factor H-related protein-5 (CFHR5), a member of the human factor H protein family, is significantly elevated in patients with AS compared to other rheumatic diseases. However, the pathophysiological mechanism underlying new bone formation by CFHR5 is not fully understood. In this study, we revealed that CFHR5 and proinflammatory cytokines (TNF, IL-6, IL-17A, and IL-23) were elevated in the AS group compared to the HC group. Correlation analysis revealed that CFHR5 levels were not significantly associated with proinflammatory cytokines, while CFHR5 levels in AS were only positively correlated with the high CRP group. Notably, treatment with soluble CFHR5 has no effect on clinical arthritis scores and thickness at hind paw in curdlan-injected SKG, but significantly increased the ectopic bone formation at the calcaneus and tibia bones of the ankle as revealed by micro-CT image and quantification. Basal CFHR5 expression was upregulated in AS-osteoprogenitors compared to control cells. Also, treatment with CFHR5 remarkedly induced bone mineralization status of AS-osteoprogenitors during osteogenic differentiation accompanied by MMP13 expression. We provide the first evidence demonstrating that CFHR5 can exacerbate the pathological bone formation of AS. Therapeutic modulation of CFHR5 could be promising for future treatment of AS. KEY MESSAGES: Serum level of CFHR5 is elevated and positively correlated with high CRP group of AS patients. Recombinant CFHR5 protein contributes to pathological bone formation in in vivo model of AS. CFHR5 is highly expressed in AS-osteoprogenitors compared to disease control. Recombinant CFHR5 protein increased bone mineralization accompanied by MMP13 in vitro model of AS.

Angiotensin receptor blockers, but not angiotensin-converting enzyme inhibitors, inhibit abnormal bone changes in spondyloarthritis.

Spondyloarthritis (SpA) is a chronic inflammatory disease that results in bone ankylosis. The tissue renin-angiotensin system (RAS) is an emerging pathway potentially implicated in SpA-associated bone changes. The aim of the present study was to determine the mechanisms underlying this relationship. Sakaguchi (SKG) mice injected with curdlan (SKGc), animal models for SpA, were treated with RAS modulators, angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis). Disease activity was assessed using clinical scores and computed tomography scans. Mouse primary bone marrow monocytes (BMMs), osteoblast (OB) progenitor cells, peripheral blood monocytes (PBMCs), and bone-derived cells (BdCs) from patients with radiographic axial SpA (r-axSpA) were used to investigate the role of RAS in SpA pathogenesis. The expression of RAS components was significantly increased in SKGc mouse joints, and ARBs significantly reduced erosion and systemic bone loss, whereas ACEis did not. Osteoclast (OC) differentiation from primary BMMs, mediated by TRAF6, was inhibited by ARBs but promoted by ACEis; the modulators also exerted opposite effects on OB differentiation. Expression of RAS molecules was higher in PBMCs and BdCs of patients with r-axSpA than in control participants. ARBs inhibited OB differentiation in the BdCs of patients with r-axSpA, whereas ACEis did not. Neither ARBs nor ACEis affected OB differentiation in the control participants. In SpA, a condition characterized by RAS overexpression, ARBs, but not ACEis, inhibited OC and OB differentiation and bone progression. The findings should be taken into account when treating patients with SpA using RAS modulators.

Elevated BMPR2 expression amplifies osteoblast differentiation in ankylosing spondylitis.

Objective: Bone morphogenetic protein receptor type 2 (BMPR2) has been associated with radiographic changes in ankylosing spondylitis (AS), but further characterization of the cellular signaling pathway in osteoprogenitor (OP) is not clearly understood. The aim of this study was to investigate the expression of BMPR2 and bone morphogenetic protein 2 (BMP2)-mediated responsibility in AS. Methods: We collected 10 healthy control (HC) and 14 AS-OPs derived from facet joints. Subsequently, we then conducted RNA sequencing with two samples per group and selected BMP-related genes. Facet joint tissues and derived primary OPs were evaluated by validation of selected RNA sequencing data, immunohistochemistry, and comparison of osteogenic differentiation potential. Results: Based on RNA-sequencing analysis, we found that BMPR2 expression is higher in AS-OPs compared to in HC-OPs. We also validated the increased BMPR2 expression in facet joint tissues with AS and its derived OPs in messenger RNA and protein levels. Additionally, primary AS-OPs showed much greater response to osteogenic differentiation induced by BMP2 and a higher capacity for smad1/5/8-induced RUNX2 expression compared to HCs. Conclusion: The expression of BMPR2 was found to be significantly increased in facet joint tissues of patients with AS. These findings suggest that BMPR2 may play a role in the BMP2-mediated progression of AS.

Re-stooping after Corrective Osteotomy in Patients with Ankylosing Spondylitis.

Background: Corrective osteotomy is an effective surgery for correcting posture in patients with ankylosing spondylitis (AS). Despite satisfactory correction, some patients experience re-stooping during follow-up. However, there have been no studies on re-stooping in AS. We aimed to analyze the factors that affect re-stooping. Methods: Fifty patients (50 cases) who underwent thoracolumbar corrective osteotomy for AS from March 2006 to April 2018 were analyzed. We defined re-stooping as global kyphosis that recurs after corrective osteotomy. The patients were divided into two groups based on the ratio of correction loss: non-re-stooping group (N group) and re-stooping group (R group). We analyzed the demographic data and radiological parameters, such as modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), sagittal vertical axis, and various angles. We also investigated the factors affecting re-stooping by analyzing the correlation between the ratio of correction loss and various factors. Results: A significant difference was seen in the change in the mSASSS from before surgery to the last follow-up between the N group (2.87 ± 3.08) and the R group (9.20 ± 5.44). In multivariate analysis, only the change in the mSASSS from before surgery to the last follow-up was significantly correlated with the ratio of correction loss. Conclusions: Thoracolumbar corrective osteotomy seems to provide high satisfaction among patients with AS but can lead to re-stooping during follow-up. The change in mSASSS was related with re-stooping in the current study. We recommend active rehabilitative exercises and appropriate medication depending on the patient's condition, which may help delay the postoperative progression of AS.

Extracellular PPM1A promotes mineralization of osteoblasts differentiation in ankylosing spondylitis via the FOXO1A-RUNX2 pathway.

Protein phosphatase magnesium-dependent 1A (PPM1A), serine/threonine protein phosphatase, in sera level was increased in patients with ankylosing spondylitis (AS). Preosteoblasts were differentiated actively to matured osteoblasts by intracellular PPM1A overexpression. However, it was unclear whether extracellular PPM1A contributes to the excessive bone-forming activity in AS. Here, we confirmed that PPM1A and runt-related transcription factor 2 (RUNX2) were increased in facet joints of AS. During osteoblasts differentiation, exogenous PPM1A treatment showed increased matrix mineralization in AS-osteoprogenitor cells accompanied by induction of RUNX2 and factor forkhead box O1A (FOXO1A) protein expressions. Moreover, upon growth condition, exogenous PPM1A treatment showed an increase in RUNX2 and FOXO1A protein expression and a decrease in phosphorylation at ser256 of FOXO1A protein in AS-osteoprogenitor cells, and positively regulated promoter activity of RUNX2 protein-binding motif. Mechanically, exogenous PPM1A treatment induced the dephosphorylation of transcription factor FOXO1A protein and translocation of FOXO1A protein into the nucleus for RUNX2 upregulation. Taken together, our results suggest that high PPM1A concentration promotes matrix mineralization in AS via the FOXO1A-RUNX2 pathway.

Platelet-Derived Growth Factor B Is a Key Element in the Pathological Bone Formation of Ankylosing Spondylitis.

Enthesophyte formation plays a crucial role in the development of spinal ankylosis in ankylosing spondylitis (AS). We aimed to investigate the role of platelet-derived growth factor B (PDGFB) in enthesophyte formation of AS using in vitro and in vivo models and to determine the association between PDGFB and spinal progression in AS. Serum PDGFB levels were measured in AS patients and healthy controls (HC). Human entheseal tissues attached to facet joints or spinous processes were harvested at the time of surgery and investigated for bone-forming activity. The impact of a pharmacological agonist and antagonist of platelet-derived growth factor B receptor (PDGFRB) were investigated respectively in curdlan-treated SKG mice. PDGFB levels were elevated in AS sera and correlated with radiographic progression of AS in the spine. Mature osteoclasts secreting PDGFB proteins were increased in the AS group compared with HC and were observed in bony ankylosis tissues of AS. Expression of PDGFRB was significantly elevated in the spinous enthesis and facet joints of AS compared with controls. Moreover, recombinant PDGFB treatment accelerated bone mineralization of enthesis cells, which was pronounced in AS, whereas PDGFRB inhibition efficiently reduced the PDGFB-induced bone mineralization. Also, PDGFRB inhibition attenuated the severity of arthritis and enthesophyte formation at the joints of curdlan-treated SKG mice. This study suggests that regulating PDGFB/PDGFRB signaling could be a novel therapeutic strategy to block key pathophysiological processes of AS. © 2022 American Society for Bone and Mineral Research (ASBMR).

Clinical and genetic factors associated with radiographic damage in patients with ankylosing spondylitis.

OBJECTIVES: To identify clinical and genetic factors associated with severe radiographic damage in patients with ankylosing spondylitis (AS). METHODS: We newly generated genome-wide single nucleotide polymorphism data (833K) for 444 patients with AS. The severity of radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). To identify clinical and genetic factors associated with severe radiographic damage, multiple linear regression analyses were performed. Human AS-osteoprogenitor and control-osteoprogenitor cells were used for functional validation. RESULTS: The significant clinical factors of final mSASSS were baseline mSASSS (ß=0.796, p=3.22×10-75), peripheral joint arthritis (ß=-0.246, p=6.85×10-6), uveitis (ß=0.157, p=1.95×10-3), and smoking (ß=0.130, p=2.72×10-2) after adjusting for sex, age and disease duration. After adjusting significant clinical factors, the Ryanodine receptor 3 (RYR3) gene was associated with severe radiographic damage (p=1.00×10-6). For pathway analysis, the PI3K-Akt signalling pathway was associated with severe radiographic damage in AS (p=2.21×10-4, false discovery rate=0.040). Treatment with rhodamine B, a ligand of RYR3, dose-dependently induced matrix mineralisation of AS osteoprogenitors. However, the rhodamine B-induced accelerated matrix mineralisation was not definitive in control osteoprogenitors. Knockdown of RYR3 inhibited matrix mineralisation in SaOS2 cell lines. CONCLUSIONS: This study identified clinical and genetic factors that contributed to better understanding of the pathogenesis and biology associated with radiographic damage in AS.

Biomechanical comparison of the femoral neck system and the dynamic hip screw in basicervical femoral neck fractures.

The purpose of this study was to compare the fixation stability of proximal fragments and the mechanical characteristics in proximal femur models of basicervical femoral neck fracture fixed by the femoral neck system (FNS) versus the dynamic hip screw. The mean axial stiffness was 234 ± 35 N/mm in the FNS group and 253 ± 42 N/mm in the DHS group, showing no significant difference (p = 0.654). Mean values for x-axis rotation, y-axis rotation, and z-axis rotation after cycle load were 2.2 ± 0.5°, 6.5 ± 1.5°, and 2.5 ± 0.6°, respectively, in the FNS group and 2.5 ± 0.7°, 5.8 ± 2.1°, and 2.2 ± 0.9°, respectively, in the DHS group, showing no significant differences (p = 0.324, p = 0.245, and p = 0.312, respectively). The mean values of cranial and axial migration of screws within the femoral head were 1.5 ± 0.3 and 2.1 ± 0.2 mm, respectively, in the FNS group and 1.2 ± 0.3 and 2.4 ± 0.3 mm, respectively, in the DHS group, showing no significant differences (p = 0.425 and p = 0.625, respectively). The average failure load at vertical load was 1342 ± 201 N in the FNS group and 1450 ± 196 N in the DHS group, showing no significant difference (p = 0.452). FNS fixation might provide biomechanical stability comparable to that of DHS for treating displaced basicervical femoral neck fractures in young adults.

WNT16 elevation induced cell senescence of osteoblasts in ankylosing spondylitis.

BACKGROUND: WNT16 is critical for bone homeostasis, but the effect of WNT16 in ankylosing spondylitis (AS) is still unknown. Here, we investigated whether WNT16 influences bone formation and pathophysiological changes of AS in an in vitro model. METHODS: The bone tissue from the facet joints was obtained from seven disease control and seven AS patients. Primary osteoprogenitor cells of the facet joints were isolated using an outgrowth method. Isolated osteoprogenitor cells from both control and AS tissues were analyzed by microarray, RT-qPCR, immunoblotting, and immunohistochemistry. The bone-forming activity of osteoprogenitor cells was assessed by various in vitro assays. ß-galactosidase staining and senescence-associated secretory phenotype (SASP) using RT-qPCR were used to assess cell senescence. RESULTS: In microarray analysis, WNT16 expression was significantly elevated in AS osteoprogenitor cells compared to the control. We also validated that WNT16 expression was elevated in AS-osteoprogenitor cells and human AS-bone tissues. WNT16 treatment inhibited bone formation in AS-osteoprogenitor cells but not in the control. Intriguingly, AS-osteoprogenitor cells were stained markedly with ß-galactosidase for cell senescence in WNT16 treatment. Furthermore, in an H2O2 stress-induced premature senescence condition, WNT16 treatment increased cell senescence in AS-osteoprogenitor cells and WNT16 treatment under the H2O2 stress condition showed an increase in p21 protein and SASP mRNA expression. The WNT16-induced SASP expression in AS-osteoprogenitor cells was reduced in WNT16 knockdown cultures. CONCLUSION: WNT16 is highly expressed in AS and WNT16 treatment facilitated cell senescence in AS-osteoprogenitor cells during osteoblast differentiation accompanied by suppression of bone formation. The identified role of WNT16 in AS could influence bone loss in AS patients.

Macrophage migration inhibitory factor drives pathology in a mouse model of spondyloarthritis and is associated with human disease.

Spondyloarthritis (SpA), a type 3 immunity-mediated inflammatory arthritis, is a systemic rheumatic disease that primarily affects the joints, spine, gut, skin, and eyes. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine, yet MIF's pathological role in SpA is unknown. Here, we observed that the expression of MIF and its receptor CD74 is increased in blood and tissues of curdlan (ß-glucan)­treated SKG mice, a mouse model of SpA. We found that neutrophils substantially expanded and produced MIF in curdlan-treated SKG mice and that human neutrophils from SpA patients secreted higher concentrations of MIF compared to healthy individuals. Although genetic deletion of Mif (Mif−/−) substantially suppressed the severity of SpA features, adoptive transfer of inflammatory neutrophils induced SpA pathology in curdlan-treated Mif−/− SKG mice; in contrast, blocking the function of neutrophils with anti­Gr-1 antibody suppressed the curdlan-induced SpA-like phenotype. We also determined that systemic MIF overexpression was sufficient to induce SpA-like clinical features in SKG mice with enhanced type 3 immunity, whereas SKG mice treated with a MIF antagonist prevented or attenuated curdlan-induced SpA manifestations. Mechanistically, we identified that MIF intensifies type 3 immunity by boosting human and mouse T regulatory cell (Treg) acquisition of a TH17 cell­like phenotype, including the up-regulation of interleukin-17 (IL-17) and IL-22 in vitro. Tregs in blood and synovial fluids from SpA patients have a pathologic TH17 phenotype. These results indicate that MIF is a crucial regulator and a potential therapeutic target in type 3 immunity-mediated arthritis.

Survival analysis and risk factors of new vertebral fracture after vertebroplasty for osteoporotic vertebral compression fracture.

BACKGROUND CONTEXT: Although risk factors of new adjacent vertebral fracture (AVF) and remote vertebral fracture (RVF) after vertebroplasty may differ, research on this topic is lacking. PURPOSE: To determine the natural course of new vertebral fractures after vertebroplasty for osteoporotic vertebral compression fracture (OVCF) and to analyze each risk factor for understanding the incidence of AVF and RVF. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: The study subjects included 205 patients who received vertebroplasty for OVCF and were followed-up for at least 1-year. OUTCOME MEASURES: Data on factors that could affect the occurrence of vertebral fractures, such as age, body mass index, and bone density, were collected from the patients' medical records. Fracture pattern, fracture location, sagittal imbalance, degree of segmental kyphosis after vertebroplasty, cement distribution, and cement leakage were radiologically examined. METHODS: xDuring the follow-up period, any newly developed vertebral fractures were identified. We analyzed whether the time of occurrence differed between AVF and RVF by performing a survival analysis and each risk factor separately. RESULTS: New vertebral fractures occurred in 47 patients (22.9%) after vertebroplasty, AVF occurred in 21 patients (10.2%), and RVF occurred in 26 patients (12.7%). The onset time of AVF was 6.2±1.8 months after vertebroplasty, showing a significant difference from that of RVF, which was 15.2±1.8 months (p<.001). In the univariate analysis, the risk factors of AVF included severe osteoporosis (T-score<-3.0), vertebroplasty in the thoracolumbar junction, sagittal imbalance, and segmental kyphosis angle >15° (p=0.029, p=0.033, p=0.001, and p=0.021, respectively). The risk factors of RVF included severe osteoporosis (T-score <-3.0) and sagittal imbalance (p=0.013 and p=0.004). In the multivariate analysis, the risk factors of AVF included vertebroplasty in the thoracolumbar junction and sagittal imbalance (hazard ratio=3.34, p=0.032 and hazard ratio=4.05, p=0.008), and those of RVF included only sagittal imbalance (hazard ratio=2.66, p=0.024). CONCLUSON: After vertebroplasty for OVCF, a significant difference in the meantime of occurrence was found; it took 6 months for AVF and 15 months for RVF to develop. Vertebroplasty in the thoracolumbar junction was identified as a risk factor for AVF, whereas sagittal imbalance was a risk factor of both AVF and RVF.

The TNF-NF-kB-DKK1 Axis Promoted Bone Formation in the Enthesis of Ankylosing Spondylitis.

Objective: This study aimed to determine the serum Dickkopf 1 (DKK1) levels in ankylosing spondylitis (AS) patients and decipher the mechanism of tumor necrosis factor (TNF)-mediated DKK1 regulation in human AS enthesis cells. Methods: The sera were obtained from 103 patients with AS and 30 healthy controls (HCs) The enthesis of facet joints were obtained from 4 AS patients and 5 controls The serum levels of DKK1 were measured using ELISA and compared between AS and HCs The impact of TNF on DKK1 expression in human primary spinal enthesis cells was evaluated using various molecular biology techniques and bone formation indicators. Results: AS patients showed higher serum DKK1 levels than HCs after adjusting for age (9174 [6153∼1,3100] pg/mL vs 8262 [6703∼9278] pg/mL, p=0043) TNF treatment promoted bone formation and DKK1 expression in both control enthesis cells and those of AS This enhanced bone formation by TNF was pronounced in AS-enthesis than those of controls Mechanically, TNF induced NF-kB activation upregulates the DKK1 transcript level While, NF-kB inhibitor led to downregulate DKK1 expression in the enthesis Besides, DKK1 overexpression promoted bone formation in enthesis. Conclusion: TNF induced DKK1 expression in the enthesis through NF-kB activation TNF-induced DKK1 expression may play a bone formation in the radiologic progression of ankylosing spondylitis.

STAT3 phosphorylation inhibition for treating inflammation and new bone formation in ankylosing spondylitis.

OBJECTIVE: AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS. METHODS: Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT. RESULTS: In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively). CONCLUSION: Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.

Autoantibodies against Protein Phosphatase Magnesium-Dependent 1A as a Biomarker for Predicting Radiographic Progression in Ankylosing Spondylitis Treated with Anti-Tumor Necrosis Factor Agents.

BACKGROUND: Patients with ankylosing spondylitis (AS) have increased levels of protein phosphatase magnesium-dependent 1A (PPM1A) and autoantibodies. We evaluated the usefulness of serum anti-PPM1A antibodies as a biomarker for AS. METHODS: Serum samples from 58 AS patients were obtained from a multicenter registry prior to the initiation of anti-TNF agents. The serum levels of anti-PPM1A antibodies were measured using ELISA. Spinal radiographic progression was defined as an increase in the modified stoke ankylosing spondylitis spinal score (mSASSS) by ≥2 units or a newly developed syndesmophyte. The role of exogenous PPM1A on bone mineralization was evaluated using primary osteoprogenitors acquired from patients with AS and non-inflammatory controls. RESULTS: The baseline levels of anti-PPM1A antibodies and mSASSS were higher in the radiographic progression group than in the non-progression group. In logistic regression analysis, baseline mSASSS and serum anti-PPM1A antibodies were associated with a higher risk of progression. The level of anti-PPM1A antibodies for predicting progression had an AUC of 0.716 (cut-off value: 43.77 ng/mL). PPM1A stimulation increased matrix mineralization in AS-osteoprogenitors but not in controls. CONCLUSION: Along with mSASSS, the serum levels of anti-PPM1A antibodies might be useful as a predictor of radiographic progression after treatment with anti-TNF agents.

Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is characteristically male-predominant, and progressive spinal ankylosis affects male patients more severely; however, the hormonal effects in males with AS are poorly understood. METHODS: In the present study, the regulatory effects of dutasteride, a 5-α reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (DHT), were examined in curdlan-administered male SKG mice to determine spinal bone formation, bone metabolism-related markers, and interleukin (IL)-17A cytokine and T cell populations. In addition, the effects of DHT on primary osteoprogenitors from the facet joints of AS patients were assessed based on osteoblast-related parameters. DHT level was measured, and the correlation with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was analyzed in AS patients. RESULTS: In curdlan-administered SKG mice, dutasteride treatment resulted in an increased accumulation of hydroxyapatite in the spine which was positively correlated with serum IL-17A levels. In the analysis of bone metabolism-related molecules, a decrease in sclerostin levels was observed in the sera in the dutasteride group. Continuous exposure to DHT resulted in fewer calcium deposits in AS osteoprogenitors during osteoblast differentiation. DHT-treated AS osteoprogenitors showed decreased osteocalcin and increased DKK1 and SOST1 mRNA expression, supporting the results of the in vivo experiments. Treatment with dutasteride upregulated bone formation in the spine of curdlan-administered SKG mice and DHT treatment downregulated osteoblast differentiation in vitro. CONCLUSIONS: Treatment with dutasteride affected the bone formation in the spine of curdlan-treated SKG mice, and DHT treatment attenuated osteoblast differentiation in vitro. Therefore, contrary to what could be expected if osteoblasts contributed to spinal ankylosis, DHT inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients.

Sarcopenia and fatty degeneration of paraspinal muscle associated with increased sagittal vertical axis in the elderly: a cross-sectional study in 71 female patients.

PURPOSE: Both increased sagittal vertical axis (SVA) and sarcopenia affect performance of daily activities and morbidity in the elderly; however, little is known regarding their relationship. The aim of this study was to analyze the association between sarcopenia and increased SVA. METHODS: This retrospective study included 71 female patients aged between 60 and 85 years. Entire-spine radiography was used to measure radiological parameters. A bioelectrical impedance analyzer was used to measure the skeletal muscle mass index (SMI). Gait velocity (GV) and hand grip strength (HGS) were examined as well. Lumbar spine magnetic resonance imaging was employed to measure the functional cross-sectional area (FCSA) and fat signal fraction (FSF) of the paraspinal muscle as well. The subjects were divided into two groups according to the SVA (group I; SVA > 50 mm and group II; SVA ≤ 50 mm). RESULTS: The group I showed lower GV, HGS, and SMI than the group II (p < 0.001, < 0.001, and = 0.001, respectively). The prevalence of sarcopenia was higher in the group I (56.7%) than in the group II (17.1%) (p = 0.001). The group I also showed lower FCSA and higher FSF than the group II (p < 0.001). In multivariate analysis, the FSF (odds ratio 1.308, p = 0.004) and HGS (odds ratio 0.792, p = 0.023) were correlated with increased SVA. In addition, the BMI (odds ratio 0.756, p = 0.037), SVA (odds ratio 1.051, p = 0.031), and FCSA (odds ratio 0.995, p = 0.012) were correlated with sarcopenia. CONCLUSION: Sarcopenia and fatty degeneration of paraspinal muscle are closely related to increased SVA in the elderly.

Acetabular cup migration after primary cementless total hip arthroplasty in rheumatoid arthritis and its influencing factors: a comparative study with osteoarthritic hip.

PURPOSE: To compare the radiographic migration profiles of primary cementless total hip arthroplasty (THA) between patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). METHODS: A total of 197 patients (215 hips) who underwent cementless THA for RA or OA between January 2001 and January 2013 and followed up for a minimum of 5.5 years were included. Ninety-four RA patients (109 hips) were compared with 103 OA patients (106 hips). Radiological evaluation was performed for acetabular cup loosening, and cup migration was measured using Einzel-Bild-Röntgen-Analyse (EBRA) software. Multiple variables were assessed to identify influencing factors for cup migration. RESULTS: Early cup migration was observed in 13 hips (11.9%) in the RA group and four hips (3.8%) in the OA group, showing a significant difference (p = 0.041). Acetabular cup loosening occurred in three cups (2.8%) in the RA group and in one cup (0.9%) in the OA group, showing no significant difference (p = 0.321). Total cup migration was higher in the RA group (2.62 mm) than in the OA group (1.44 mm, p = 0.005). Total cup migration was significantly higher in patients aged < 50 years than in those aged > 50 years (p = 0.005). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody influenced total cup migration. Patients with seropositive RA showed significantly higher total cup migration and early cup migration incidence than those with seronegative RA (p = 0.005, p = 0.038, respectively). CONCLUSIONS: Acetabular cups in primary cementless THAs of RA patients were less stable in terms of cup migration compared with that of OA patients.

Efficacy of risedronate with cholecalciferol on bone mineral density in Korean patients with osteoporosis.

The efficacy of once-weekly risedronate with and without cholecalciferol in bone mineral density (BMD) in Korean patients with osteoporosis was compared. After 12 months, both spine and hip BMD increased significantly in both groups, but there was no significant difference between two groups. INTRODUCTION: This study investigated the efficacy and safety of once-weekly risedronate with and without cholecalciferol in BMD in Korean patients with osteoporosis. METHODS: This was a prospective, 12-month, randomized, open-labeled, actively controlled trial involving 41 hospitals. A total of 841 subjects with osteoporosis were randomized to once-weekly risedronate (35 mg) and cholecalciferol (5600 IU) in a single pill (RSD+, n = 642) or once-weekly risedronate (35 mg) alone (RSD, n = 199). BMD was measured via dual-energy X-ray absorptiometry at the lumbar spine and hip, and the serum levels of 25-hydroxy vitamin D (25(OH) D), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were assayed at baseline and after 12 months of treatment. RESULTS: After 12 months, the lumbar spine, femoral neck, and total hip BMD increased significantly in both groups; there was no significant difference between two groups. Women in the RSD+ group exhibited significantly increased lumbar spine BMD, and subjects with previous fracture history in the RSD+ group had significantly increased total hip BMD compared with the RSD group. The serum 25(OH) D level increased significantly in the RSD+ group. The serum PTH level decreased in the RSD+ group but increased in the RSD group. The serum ALP level significantly decreased in both groups; there was no significant difference between two groups. CONCLUSIONS: A once-weekly pill containing risedronate and cholecalciferol had the equivalent antiresorptive efficacy on BMD compared with risedronate alone and improved 25(OH) D serum levels after 12 months of treatment without significant adverse events in Korean patients with osteoporosis.

Psychological Changes and Employment Outcomes After Kyphosis Correction in Patients With Ankylosing Spondylitis.

STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate the psychological changes and employment outcomes following corrective osteotomy in patients with ankylosing spondylitis (AS). SUMMARY OF BACKGROUND DATA: To date, no study has investigated the changes in psychological status and subsequent improvement in employment outcome after correction of kyphotic deformities in patients with AS. METHODS: This study included 48 patients with AS who underwent corrective osteotomy for severe kyphotic deformity. Sagittal alignment was assessed radiographically. Clinical status was evaluated using the Short Form-36 Health Survey, psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS), and employment outcomes were assessed using the Lam Employment Absence and Productivity Scale (LEAPS). The degree of postoperative sagittal alignment correction was measured, and changes in clinical and employment outcomes and psychological status were evaluated. The relationship between the degree of sagittal alignment correction and each evaluation item was analyzed. RESULTS: Following postoperative sagittal alignment correction, all patients could stand erect and look straight. Significant improvements were observed in the clinical and employment outcomes, as well as in patients' psychological status. The degree of sagittal vertical axis correction was significantly correlated with the HADS depression and the LEAPS total scores. The degree of correction of the chin-brow vertical angle was significantly correlated with the Short Form-36 mental health score, the HADS depression and anxiety scores, and the LEAPS total and productivity subscores. Notably, the improvement in the HADS depression score was significantly correlated with the LEAPS total score. CONCLUSION: This study demonstrated the psychological changes and subsequent improvement in employment outcomes after corrective osteotomy in patients with AS. The degree of sagittal alignment correction was correlated with improvements in psychological status and employment outcomes. LEVEL OF EVIDENCE: 4.