Changes in Testing and Treatment Methods in Osteoporosis Care.

Osteoporosis treatment plays a crucial role in preventing fractures, particularly in bedridden patients. We conducted a questionnaire survey presenting hypothetical clinical cases in 2015 and 2020 to investigate trends over a 5-year period. The target population included physicians working in clinics and hospitals within our neighbourhood. The cases were presented, and the questionnaire was administered in a confidential format. The orthopaedic surgeons were matched for age and practice, resulting in 74 cases being included in the analysis. Comparing the 2015 and 2020 results, we observed a notable increase in physicians who would perform "bone mineral density measurements of the lumbar spine and hip." Furthermore, there was a significant rise in the percentage of respondents willing to test for bone metabolic markers, such as serum type I collagen cross-linked N-telopeptide (NTX), procollagen I N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b (TRACP-5b). Regarding therapeutic agents, bisphosphonates decreased in usage, whereas parathyroid hormone and romosozumab witnessed an increase. In conclusion, the percentage of physicians requesting bone mineral density measurements of the lumbar spine and hip increased over the five-year period. In addition, more physicians chose to utilise bone metabolic markers due to their ease of measurement through blood tests and reduced diurnal variation. Finally, there was a marked trend towards the administration of drugs capable of rapidly and effectively increasing bone mineral density at an early stage of treatment.

Relationship between sacral-abdominal wall distance, movement performance, and spinal alignment in osteoporosis: a retrospective study.

BACKGROUND: Aging is associated with muscle atrophy, as typified by sarcopenia. Loss of abdominal muscle strength can cause abdominal wall laxity. The purpose of this study was to investigate the relationship between the sacral vertebra-abdominal wall distance (SAD) and movement performance using a simple lateral spine X-ray image for measuring the SAD. METHODS: In this retrospective study, we included women aged ≥ 65 years who were attending the outpatient clinic for osteoporosis at our hospital. A total of 287 patients (mean age ± SD, 76.8 ± 7.1 years) with measured SAD were included in the analysis. Patients were divided into two groups based on SAD cutoff (160 mm) and age (75 years), respectively. The patients were examined using the two-foot 20 cm rise test, 3 m Timed Up and Go (TUG) test, two-step test, open-eyed one-leg standing time, and spinal alignment. Normally distributed data are expressed as means (standard deviations) and non-normally distributed data as medians (interquartile range), depending on the results of the Kolmogorov-Smirnov test. Student's t-test and χ2 test were used for between-group comparisons. Regression analysis was performed with SAD as the objective variable. A two-sided p < 0.05 was considered statistically significant. RESULTS: The shorter SAD group performed better in the two-step test, TUG test, and open-eyed one-leg standing time (p < 0.001) as well as in the two-foot 20 cm rise test (p < 0.01) compared to the longer SAD group. Spinal alignment was better in the shorter SAD group than in the longer SAD group, with a shorter sagittal vertical axis (p < 0.001), smaller pelvic tilt (p < 0.001), and greater sacral slope (p < 0.05). CONCLUSION: SAD was associated with posterior pelvic tilt and movement performance parameters. In addition to testing for osteoporosis, movement performance parameters should be evaluated in women with osteoporosis who are aged ≥ 65 and have greater SAD (≥ 160 mm in this study). The SAD is a new assessment method, and further research is required to verify its validity and reproducibility. This is the first attempt to determine how age and SAD affect movement performance in older adults.

J-domain proteins: From molecular mechanisms to diseases.

J-domain proteins (JDPs) are the largest family of chaperones in most organisms, but much of how they function within the network of other chaperones and protein quality control machineries is still an enigma. Here, we report on the latest findings related to JDP functions presented at a dedicated JDP workshop in Gdansk, Poland. The report does not include all (details) of what was shared and discussed at the meeting, because some of these original data have not yet been accepted for publication elsewhere or represented still preliminary observations at the time.

Radiation-induced bone loss in mice is ameliorated by inhibition of HIF-2α in skeletal progenitor cells.

Radiotherapy remains a common treatment modality for cancer despite skeletal complications. However, there are currently no effective treatments for radiation-induced bone loss, and the consequences of radiotherapy on skeletal progenitor cell (SPC) survival and function remain unclear. After radiation, leptin receptor-expressing cells, which include a population of SPCs, become localized to hypoxic regions of the bone and stabilize the transcription factor hypoxia-inducible factor-2α (HIF-2α), thus suggesting a role for HIF-2α in the skeletal response to radiation. Here, we conditionally knocked out HIF-2α in leptin receptor-expressing cells and their descendants in mice. Radiation therapy in littermate control mice reduced bone mass; however, HIF-2α conditional knockout mice maintained bone mass comparable to nonirradiated control animals. HIF-2α negatively regulated the number of SPCs, bone formation, and bone mineralization. To test whether blocking HIF-2α pharmacologically could reduce bone loss during radiation, we administered a selective HIF-2α inhibitor called PT2399 (a structural analog of which was recently FDA-approved) to wild-type mice before radiation exposure. Pharmacological inhibition of HIF-2α was sufficient to prevent radiation-induced bone loss in a single-limb irradiation mouse model. Given that ~90% of patients who receive a HIF-2α inhibitor develop anemia because of off-target effects, we developed a bone-targeting nanocarrier formulation to deliver the HIF-2α inhibitor to mouse bone, to increase on-target efficacy and reduce off-target toxicities. Nanocarrier-loaded PT2399 prevented radiation-induced bone loss in mice while reducing drug accumulation in the kidney. Targeted inhibition of HIF-2α may represent a therapeutic approach for protecting bone during radiation therapy.

Pregnancy- and lactation-associated osteoporosis in the mother after the first and second children: A case report.

INTRODUCTION: This study reports an unusual experience of a mother who may have developed birth-related osteoporosis after each of the births of her two children. PRESENTATION OF CASE: A 31-year-old woman presented with lumbar back pain. She had given birth to her first child through vaginal delivery 4 months prior and was breastfeeding. Magnetic resonance imaging showed multiple fresh vertebral fractures, but continued breastfeeding resulted in further loss of bone density. The bone mineral density recovered after weaning. The patient gave birth to a second child three years after the first child's birth. She opted to discontinue breastfeeding after the detection of repeated instances of significant bone loss. No new vertebral fractures have occurred in the 9 years since the patient's initial visit to our clinic. DISCUSSION: We describe a case where a mother experienced multiple episodes of rapid bone loss following childbirth. Bone health evaluation at an early stage following childbirth may be effective for preventing future bone fractures. CONCLUSION: It is desirable to develop a team and guidelines for treating osteoporosis associated with pregnancy and lactation and for the next pregnancy and delivery.

Distal junctional failure after corrective surgery without pelvic fixation for thoracolumbar junctional kyphosis due to osteoporotic vertebral fracture.

BACKGROUND: Thoracolumbar junctional kyphosis (TLJK) due to osteoporotic vertebral fracture (OVF) negatively impacts patients' quality of life. The necessity of pelvic fixation in corrective surgery for TLJK due to OVF remains controversial. This study aimed to: 1) evaluate the surgical outcomes of major corrective surgery for thoracolumbar junctional kyphosis due to osteoporotic vertebral fracture, and 2) identify the risk factors for distal junctional failure to identify potential candidates for pelvic fixation. METHODS: Patients who underwent surgical correction (fixed TLJK>40°, OVF located at T11-L2, the lowermost instrumented vertebra at or above L5) were included. Sagittal vertical axis, pelvic tilt, pelvic incidence, thoracic kyphosis, lumbar lordosis (L1-S1), local kyphosis, and lower lumbar lordosis (L4-S1) were assessed. Proximal and distal junctional kyphosis (P/DJK) and failures (P/DJF) were evaluated. Pre/postoperative spinopelvic parameters were compared between DJF and non-DJF patients. RESULTS: Thirty-one patients (mean age: 72.3 ± 7.9 years) were included. PJK was observed in five patients (16.1%), while DJK in 11 (35.5%). Twelve cases (38.7%) were categorized as failure. Among the patients with PJK, there was only one patient (20%) categorized as PJF and required an additional surgery. Contrary, all of eleven patients with DJK were categorized as DJF, among whom six (54.5%) required additional surgery for pelvic fixation. In comparisons between DJF and non-DJF patients, there was no significant difference in pre/postoperative LK (pre/post, p = 0.725, p = 0.950). However, statistically significant differences were observed in the following preoperative alignment parameters: SVA (p = 0.014), LL (p = 0.001), LLL (p = 0.006), PT (p = 0.003), and PI-LL (p < 0.001). CONCLUSIONS: Spinopelvic parameters, which represent the compensatory function of lumbar hyperlordosis and pelvic retroversion, have notable impacts on surgical outcomes in correction surgery for TLJK due to OVF. Surgeons should consider each patient's compensatory function when choosing a surgical approach.

Knee meniscus regeneration using autogenous injection of uncultured adipose tissue-derived regenerative cells.

Introduction: The low healing potential of mature menisci necessitates traditional surgical removal (meniscectomy) to eliminate acute or chronic degenerative tears. However, removal of meniscal tissue is main factor causing osteoarthritis. Adipose tissue-derived regenerative cells (ADRCs), a heterogeneous cell population that includes multipotent adipose-derived stem cells and other progenitor cells, were easily isolated in large amounts from autologous adipose tissue, and same-day processing without culture or expansion was possible. This study investigated the regenerative potential of autologous ADRCs for use in meniscus defects. Methods: In 10- to 12-week-old male SD rat partial meniscectomy model, an atelocollagen sponge scaffold without or with ADRCs (5.0 × 105 cells) was injected into each meniscus defect. Reconstructed menisci were subjected to histologic, and dynamic mechanical analyses. Results: After 12 weeks, areas of regenerated meniscal tissue in the atelocollagen sponge scaffold in rats with ADRCs (64.54 ± 0.52%, P < 0.05, n = 10) were larger than in those without injection (57.96 ± 0.45%). ADRCs were shown capable of differentiating chondrocyte-like cells and meniscal tissue components such as type II collagen. Higher elastic moduli and lower fluid permeability of regenerated meniscal tissue demonstrated a favorable structure-function relationship required for native menisci, most likely in association with micron-scale porosity, with the lowest level for tissue integrity possibly reproducible. Conclusions: This is the first report of meniscus regeneration induced by injection of ADRCs. The results indicate that ADRCs will be useful in future clinical cell-based therapy strategies, including as a cell source for reconstruction of damaged knee menisci.

Comparison of pedicle screw placement accuracy between two types of imaging support (Artis Zeego versus two-dimensional fluoroscopy): a cross-sectional observational study.

BACKGROUND: The pedicle screw system is widely used in spine surgery, and it provides rigid fixation and leads to successful subsequent deformity correction and bony fusion. The standard imaging technique for pedicle screw insertion is two-dimensional images obtained from C-arm-type X-ray fluoroscopy. Artis Zeego is an emerging intraoperative imaging technique that can provide conventional two-dimensional fluoroscopic images and rapid three-dimensional fluoroscopic computed tomography reconstruction imaging. The aim of this study is to compare the insertion accuracies of PS placement using Artis Zeego and conventional 2D X-ray fluoroscopy. METHODS: In this study, we retrospectively reviewed the postoperative images of thoracolumbar fusion patients who underwent surgery using pedicle screws between 2013 and 2018. Pedicle screw malplacement was assessed using a four-grade classification by Rao et al. Misplacement rates were compared between pedicle screws assisted with Artis Zeego and two-dimensional fluoroscopy. RESULTS: A total of 1107 pedicle screws in 153 patients were inserted using Artis Zeego, and 427 pedicle screws in 80 patients were inserted using fluoroscopy. The overall perforation rate was 4.2% (46 perforations of 1106 pedicle screws) in the Artis Zeego group and 7.7% (33 perforations of 427 pedicle screws) in the fluoroscopy group. In the Artis Zeego group, 43 (3.9%) screws were classified as grade 1, and three (0.3%) screws were classified as grade 2. In the fluoroscopy group, 21 (4.9%) screws were classified as grade 1, 10 (2.3%) screws were classified as grade 2, and 2 (0.5%) screws were classified as grade 3. The use of Artis Zeego was associated with a significantly lower screw malplacement rate than was the use of fluoroscopy (p < 0.001). CONCLUSIONS: Our results demonstrated that pedicle screw placement with Artis Zeego was associated with a lower malplacement rate than was conventional two-dimensional fluoroscopy. No severe malplacement was observed in the Artis Zeego group. Thus, Artis Zeego could be a good option for improving pedicle screw accuracy.

The origins and roles of osteoclasts in bone development, homeostasis and repair.

The mechanisms underlying bone development, repair and regeneration are reliant on the interplay and communication between osteoclasts and other surrounding cells. Osteoclasts are multinucleated monocyte lineage cells with resorptive abilities, forming the bone marrow cavity during development. This marrow cavity, essential to hematopoiesis and osteoclast-osteoblast interactions, provides a setting to investigate the origin of osteoclasts and their multi-faceted roles. This Review examines recent developments in the embryonic understanding of osteoclast origin, as well as interactions within the immune environment to regulate normal and pathological bone development, homeostasis and repair.

Influence of Mutual Support on Burnout among Intensive Care Unit Healthcare Professionals.

Introduction: Burnout among healthcare professionals in intensive care units (ICUs) is a serious issue that leads to early retirement and medication errors. Their gender, lower years of experience, and lower education have been reported as risk factors. Simultaneously, mutual support-commonly referred to as "back-up behavior," in which staff members support each other-is critical for team performance. However, little is known about the influence of mutual support among ICU healthcare professionals on burnout. The U.S. Agency for Healthcare Research and Quality refers to mutual support as the involvement of team members in: assisting one another, providing and receiving feedback, and exerting assertive and advocacy behaviors when patient safety is threatened. Objective: This study aimed to verify the hypothesis that lower mutual support among ICU healthcare professionals is associated with increased probability of burnout. Methods: A web-based survey was conducted from March 4 to 20, 2021. All ICU healthcare professionals in Japan were included. An invitation was sent via the mailing list of the Japanese Society of Intensive Care Medicine and asked to mail to local communities and social network services. We measured burnout severity using the Maslach Burnout-Human Services Survey and mutual support using the TeamSTEPPS Teamwork Perceptions Questionnaire, as well as occupational background. The cutoff value for burnout was predefined and conducted logistic regression. Results: We received 335 responses, all of which were analyzed. The majority of respondents were nurses (58.5%), followed by physicians (18.5%) and clinical engineers (10.1%). The burnout group scored significantly lower on mutual support than the non-burnout group. After adjusting for covariates in a logistic regression, low mutual support was an independent factor predicting a high probability of burnout. Conclusions: This study suggests that it is important to focus on mutual support among ICU healthcare professionals to reduce the frequency of burnout.

Potential of the non-weight-bearing tunnel view in diagnosing medial meniscus posterior root tear: a pilot study of X-ray characteristics.

PURPOSE: Early detection of medial meniscus posterior root tear (MMPRT) is important in preventing the rapid onset and progression of degenerative knee disease. Diagnosis is facilitated by the availability of non-weight-bearing X-ray view, but information on the X-ray characteristics of MMPRT is scarce. Here, we conducted a pilot study of the X-ray characteristics of MMPRT on non-weight-bearing tunnel view. METHODS: We retrospectively reviewed 43 consecutive patients treated in the outpatient department for medial knee pain or popliteal pain. Patients were divided into MMPRT (21 knees) and non-MMPRT groups (22 knees). We investigated X-ray characteristics and magnetic resonance imaging findings. Femorotibial angle, posterior tibial slope, medial tibial eminence (MTE)-medial femoral condyle (MFC) distance (contralateral and affected sides, and difference between the two), medial tibiofemoral joint (MTFJ) width (contralateral and affected sides, and difference between the two), and meniscus radial dislocation between the groups were evaluated using the Mann-Whitney U test. The association between X-ray characteristics and MMPRT was determined using univariate and multivariate logistic regression analyses. RESULTS: A highly significant difference between the affected and contralateral sides was seen in MTFJ width and MTE-MFC distance on non-weight-bearing tunnel view between the MMPRT and non-MMPRT groups. Moreover, a difference in MTFJ width of <-0.575 mm and in MTE-MFC distance of >0.665 mm between the affected and contralateral sides was useful in predicting MMPRT. CONCLUSIONS: The non-weight-bearing tunnel view is useful for the initial diagnosis of MMPRT. Prospective evaluation in a larger population is warranted.

Multilayered regulation of proteome stoichiometry.

Cellular systems depend on multiprotein complexes whose functionalities require defined stoichiometries of subunit proteins. Proper stoichiometry is achieved by controlling the amount of protein synthesis and degradation even in the presence of genetic perturbations caused by changes in gene dosage. As a consequence of increased gene copy number, excess subunits unassembled into the complex are synthesized and rapidly degraded by the ubiquitin-proteasome system. This mechanism, called protein-level dosage compensation, is widely observed not only under such perturbed conditions but also in unperturbed physiological cells. Recent studies have shown that recognition of unassembled subunits and their selective degradation are intricately regulated. This review summarizes the nature, strategies, and increasing complexity of protein-level dosage compensation and discusses possible mechanisms for controlling proteome stoichiometry in multiple layers of biological processes.

Radiological features of cervical spine in dropped head syndrome: a matched case-control study.

PURPOSE: Dropped head syndrome (DHS) is presumably caused by focal myopathy in the cervical posterior muscles; however, distinguishable radiological features of the cervical spine in DHS remain unidentified. This study investigated the radiological features of the cervical spine in dropped head syndrome. METHODS: The records of DHS patients and age- and sex-matched cervical spondylotic myelopathy (CSM) patients were reviewed. Cervical spinal parameters (C2-7, C2-4, and C5-7 angles) were assessed on lateral cervical spine radiographs. Quantitative radiographic evaluation of cervical spine degeneration was performed using the cervical degenerative index (CDI), which consists of four elements: disk space narrowing (DSN), endplate sclerosis, osteophyte formation, and listhesis. RESULTS: Forty-one DHS patients were included. Statistically significant differences were noted between the upper and lower cervical spine in the sagittal angle parameters on the neutral, flexion, and extension radiographs in DHS group, whereas no significant differences were observed in CSM group. CDI comparison showed significantly higher scores of DSN in C3/4, C4/5, C5/6, and C6/7; sclerosis in C5/6 and C6/7; and osteophyte formation in C4/5, C5/6, and C6/7 in DHS group than in CSM group. Comparison of listhesis scores revealed significant differences in the upper levels of the cervical spine (C2/3, C3/4, and C4/5) between two groups. CONCLUSION: Our results demonstrated that the characteristic radiological features in the cervical spine of DHS include lower-level dominant severe degenerative change and upper-level dominant spondylolisthesis. These findings suggest that degenerative changes in the cervical spine may also play a role in the onset and progression of DHS.

Analysis of the subsequent treatment of osteoporosis by transitioning from bisphosphonates to denosumab, using quantitative computed tomography: A prospective cohort study.

PURPOSE: Denosumab reduces bone resorption and improves bone mineral density (BMD). Studies have analyzed subsequent treatment transitioning from bisphosphonates to denosumab based on dual-energy X-ray absorptiometry scanning (DXA). Quantitative computed tomography (QCT) can help assess cortical and trabecular bones separately in three dimensions without the interference of the surrounding osteophytes. In the present study, we analyzed the subsequent treatment transition from bisphosphonates to denosumab using QCT. METHODS: Thirty-two patients with postmenopausal osteoporosis to be treated with denosumab were recruited. The patients were divided into two groups (15 prior bisphosphonate and 17 naïve) based on their previous treatment. BMD of the lumbar spine and hip were evaluated by DXA and QCT at baseline and 12 months following denosumab treatment. RESULTS: The percentage change in volumetric BMD assessed by QCT at 12 months significantly improved in the naïve group compared with that in the prior bisphosphonate group. The region-specific assessment of femur at 12 months revealed that denosumab treatment was effective in both cortical and trabecular bones except the trabecular region of the prior bisphosphonate group. CONCLUSION: Our study suggests that although denosumab treatment was useful in both treatment groups, BMD increase was significantly higher in the naïve group than in the prior-bisphosphonate group. Interestingly, in the prior-bisphosphonate group, denosumab treatment was more effective in the cortical region than the trabecular region. Our study offers insights into the subsequent treatment and permits greater confidence when switching to denosumab from bisphosphonates.

The effect of denosumab on pedicle screw fixation: a prospective 2-year longitudinal study using finite element analysis.

BACKGROUND: Pedicle screw loosening is a major complication following spinal fixation associated with osteoporosis in elderly. However, denosumab is a promising treatment in patients with osteoporosis. The effect of denosumab on pedicle screw fixation is unknown. Therefore, we investigated whether denosumab treatment improves pedicle screw fixation in elderly patients with osteoporosis. METHODS: This was a 2-year prospective open-label study. From February 2015 to January 2016, we included 21 patients with postmenopausal osteoporosis who received initial denosumab treatment. At baseline, 12 months, and 24 months, we measured volumetric bone mineral density (BMD) using quantitative computed tomography (QCT) and performed CT-based finite element analysis (FEA). Finite element models of L4 vertebrae were created to analyze the bone strength and screw fixation. RESULTS: BMD increased with denosumab treatment. FEA revealed that both pullout strength of pedicle screws and compression force of the vertebra increased significantly at 12 and 24 months following denosumab treatment. Notably, pullout strength showed a stronger correlation with three-dimensional volumetric BMD around pedicle screw placement assessed by QCT (r = 0.83, at 24 months) than with two-dimensional areal BMD assessed by dual energy X-ray absorptiometry (r = 0.35, at 24 months). CONCLUSION: To our knowledge, this is the first study to reveal that denosumab treatment achieved strong pedicle screw fixation with an increase in BMD around the screw assessed by QCT and FEA; therefore, denosumab could be useful for osteoporosis treatment during spinal surgery in elderly patients with osteoporosis.

The serum 25(OH)D level and hand grip strength for fall risk assessment among osteoporotic elderly Japanese women.

We investigated the relationship between serum 25(OH)D levels, grip strength, and fall score in elderly osteoporotic women for fall risk assessment. Both low serum 25(OH)D and low grip strength were independently associated with increased fall risk. The serum 25(OH)D cutoff specific to increased fall risk was 14 mg/dL (35 nmol/L). PURPOSE: This study aimed to establish a cutoff value of serum 25-hydroxyvitamin D (25(OH)D) for fall assessment and investigate the relationship between serum 25(OH)D, grip strength, and fall score adjusted for age in osteoporotic elderly Japanese women. METHODS: This is a cross-sectional study utilizing collected data of osteoporotic elderly (age ≥65 years) female patients. A questionnaire for fall risk assessment was used, in which a score ≥ 6 was determined as increased fall risk. Serum 25(OH)D levels and grip strength were measured, and the cutoff points were calculated by receiver operating curve (ROC) analysis. Logistic regression analysis with age adjustment was conducted for potential risk factors for fall. RESULTS: After applying eligibility criteria, finally, 349 patients were enrolled. The median patient age was 77.0 years, and the mean serum 25(OH)D level was 15.6 ng/mL (36 nmol/L). Based on the ROC analysis, we defined the cutoff values of serum 25(OH)D level and grip strength as 14 ng/mL (35 nmol/L) and 15 kg, respectively. A multivariate analysis adjusted for age was conducted. Low serum 25(OH)D level and grip strength were independent risk factors for ≥6 fall risk scores. CONCLUSION: Both low serum 25(OH)D level and low grip strength were independently associated with increased fall risk score in osteoporotic elderly women. The appropriate serum 25(OH)D cutoff specific to the increased fall risk group in this population was 14 mg/dL (35 nmol/L). These findings might be used for the identification of patients with high fall risks. These results should be confirmed in other patient groups.

Thoracic Reciprocal Change Can Be Predicted Before Surgery in Adult Spinal Deformity.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Analysis of postoperative sagittal alignment of the unfused spine is lacking in patients with adult spinal deformity (ASD). The present study aims to evaluate the efficacy of the whole spine full-flexion lateral radiograph to predict the reciprocal change of the unfused spine after correction surgery. We hypothesized that the novel parameter (T1-UIV angle: angle between the upper vertebral endplate of the T1 and the upper vertebral endplate of the upper instrumented vertebra) of the preoperative whole spine full-flexion lateral radiograph is similar to that of the postoperative lateral radiograph if the patient has the ideal sagittal alignment. METHODS: Twenty-six ASD patients who underwent correction surgery with a minimum 2-year follow-up were enrolled and separated into the Ideal and Non-Ideal groups according to the Scoliosis Research Society (SRS)-Schwab classification of the final follow-up radiograph. Radiographic parameters, including T1-UIV of the preoperative whole spine full-flexion lateral radiograph, were obtained. RESULTS: Thirteen patients were included in the Ideal group and 13 were in Non-Ideal group. Preoperative T1-UIV of the whole spine full-flexion lateral radiograph exhibited significant correlations with the T1-UIV angles of the postoperative and final follow-up radiographs (r = 0.64, P < .01, y = 0.800x + 8.012, and r = 0.69, P < .01, y = 0.857x + 2.960, respectively). Interestingly, this correlation was stronger for the Ideal group (r = 0.77, P < .01, y = 1.207x - 1.517, and r = 0.89, P < .01, y = 0.986x + 0.694, respectively). CONCLUSION: A novel radiographic strategy (T1-UIV of preoperative the whole spine full-flexion lateral radiograph) could estimate the postoperative alignment of the unfused spine correctly.

Relationship Between Muscle Mass of the Lower Limbs and Falls Caused by Spinal Misalignment in Women Aged 70 Years: A Retrospective Study.

STUDY DESIGN: This retrospective study was conducted from 2015 to 2016 at the osteoporosis outpatient clinic of Showa University School of Medicine. OBJECTIVE: This study aimed to investigate the association between lower-limb muscle mass and spinal misalignment-related falls in elderly women. SUMMARY OF BACKGROUND DATA: Poor spinal alignment affects gait and balance, reducing the quality of life. Negative correlations between age-associated skeletal muscle loss and spinal sagittal alignment have been reported. MATERIALS AND METHODS: This study included 127 women with osteoporosis aged more than 70 years. The correlation between lower-limb skeletal muscle index (SMI) and sagittal vertical axis (SVA) was calculated using radiographic measurements. Spinopelvic parameters, including SVA, sacral slope, pelvic tilt (PT), pelvic incidence, and lumbar lordosis, were measured. Lower-limb SMI was measured using whole-body dual-energy x-ray absorptiometry and calculated as SMI=nonfat mass/height2. The balance function was evaluated using the single-leg stance test. Data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests; significance level was set at P<0.05. Bivariate and multivariate logistic regression analyses were used to determine correlations. RESULTS: Participants were classified into the balance and mismatch groups on the basis of a threshold SVA value of 50 mm. The groups did not differ significantly in age, height, weight, pelvic incidence, or sacral slope. Lumbar lordosis significantly decreased and PT and lower-limb SMI significantly increased in the mismatch group compared with the balance group. Lower-limb SMI was significantly correlated with increased SVA in bivariate and multivariate regression analyses. Patients with PT ≥20 degrees and SVA ≥50 mm had significantly increased lower-limb SMI. CONCLUSIONS: Increased SVA is associated with increased lower-limb SMI, which negatively affects standing balance. An increased lower-limb SMI may represent a novel compensatory mechanism for poor spinal alignment in elderly women with osteoporosis. LEVEL OF EVIDENCE: Level III.

Inhibition of hepatocyte growth factor/c-Met signalling abrogates joint destruction by suppressing monocyte migration in rheumatoid arthritis.

OBJECTIVES: To determine the expression of hepatocyte growth factor (HGF) in RA biological fluids, the role of HGF in monocyte migration and the therapeutic effect of the c-Met inhibitor savolitinib in an arthritis model mice. METHODS: HGF/c-Met expression in serum, SF and synovial tissues (STs) obtained from RA patients and controls, as well as RA fibroblast-like synoviocytes (FLSs), was evaluated by ELISA and immunostaining. To determine the function of HGF in RA SF, we preincubated RA SF with a neutralizing anti-HGF antibody and measured the chemotactic ability of a human acute monocytic leukaemia cell line (THP-1). Additionally, examinations were conducted of SKG mice treated with savolitinib for 4 weeks. RESULTS: HGF levels in serum from RA patients were significantly higher than those in the controls and were decreased by drug treatment for 24 weeks. Additionally, the HGF level in SF from RA patients was higher than that in SF from OA patients. HGF and c-Met expression was also noted in RA STs. Stimulation of RA FLSs with TNF-α increased HGF/c-Met expression in a concentration-dependent manner, and c-Met signal inhibition suppressed production of fractalkine/CX3CL1 and macrophage inflammatory protein-1α/CCL3. When HGF was removed by immunoprecipitation, migration of THP-1 in RA SF was suppressed. In SKG mice, savolitinib significantly suppressed ankle bone destruction on µCT, with an associated reduction in the number of tartrate-resistant acid phosphatase-positive osteoclasts. CONCLUSION: HGF produced by inflammation in synovium of RA patients activates monocyte migration to synovium and promotes bone destruction via a chemotactic effect and enhanced chemokine production.