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.

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.

Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes.

Proper control of gene expression levels upon various perturbations is a fundamental aspect of cellular robustness. Protein-level dosage compensation is one mechanism buffering perturbations to stoichiometry of multiprotein complexes through accelerated proteolysis of unassembled subunits. Although N-terminal acetylation- and ubiquitin-mediated proteasomal degradation by the Ac/N-end rule pathway enables selective compensation of excess subunits, it is unclear how widespread this pathway contributes to stoichiometry control. Here we report that dosage compensation depends only partially on the Ac/N-end rule pathway. Our analysis of genetic interactions between 18 subunits and 12 quality control factors in budding yeast demonstrated that multiple E3 ubiquitin ligases and N-acetyltransferases are involved in dosage compensation. We find that N-acetyltransferases-mediated compensation is not simply predictable from N-terminal sequence despite their sequence specificity for N-acetylation. We also find that the compensation of Pop3 and Bet4 is due in large part to a minor N-acetyltransferase NatD. Furthermore, canonical NatD substrates histone H2A/H4 were compensated even in its absence, suggesting N-acetylation-independent stoichiometry control. Our study reveals the complexity and robustness of the stoichiometry control system.

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.

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.

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.

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.

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.

Controlling nutritional status score predicts postoperative complications after hip fracture surgery.

BACKGROUND: Controlling Nutritional Status (CONUT) score is calculated using laboratory values, including serum albumin, total cholesterol concentration, and total lymphocyte count; it is reportedly valuable for making nutritional assessments. One advantage of CONUT score over other nutritional assessments is that it can be calculated retrospectively using only objective laboratory values. Studies demonstrated that CONUT score was a useful tool for predicting prognosis and complications in various surgical conditions. Nevertheless, few studies utilized the score as a potential predictive marker for postoperative complications among hip fracture patients. The purpose of this study was to determine the association between CONUT score and postoperative complications in hip fracture patients. METHODS: We retrospectively reviewed 211 elderly patients who underwent hip fracture surgery at a single institution from 2013 to 2018. CONUT score was calculated using preoperative routine laboratory tests for serum albumin, total cholesterol concentration, and total lymphocyte count. As potential confounders, we extracted data such as patient age, sex, fracture type, and general conditions/comorbidities, as defined by the American Society of Anesthesiologists Physical Status (ASA-PS) classification and the Charlson Comorbidity Index (CCI). Postoperative complications were defined as a Clavien-Dindo classification of 1 or more. Simple and multivaribale logistic regression analyses were performed to assess the incidence of postoperative complications as the outcome measures. RESULTS: The mean age [IQR] was 86 [80-90], and 80.1% of the reviewed patients were female. Based on the CONUT scores, 78.7% of hip fracture patients were classified as malnourished; 18% experienced postoperative complications. Simple analyses revealed significant risk factors for postoperative complications, including age, the ASA-PS, the CCI, and the CONUT score. Multivariable analysis found that CONUT score was the independent risk factor for postoperative complications (odd ratio = 1.21, 95% confidence interval = 1.01-1.45, p = 0.04). CONCLUSIONS: Preoperative CONUT scores are independently associated with the incidence of postoperative complications. CONUT score can be used for risk assessment in hip fracture patients to predict early postoperative complications.

Post-Translational Dosage Compensation Buffers Genetic Perturbations to Stoichiometry of Protein Complexes.

Understanding buffering mechanisms for various perturbations is essential for understanding robustness in cellular systems. Protein-level dosage compensation, which arises when changes in gene copy number do not translate linearly into protein level, is one mechanism for buffering against genetic perturbations. Here, we present an approach to identify genes with dosage compensation by increasing the copy number of individual genes using the genetic tug-of-war technique. Our screen of chromosome I suggests that dosage-compensated genes constitute approximately 10% of the genome and consist predominantly of subunits of multi-protein complexes. Importantly, because subunit levels are regulated in a stoichiometry-dependent manner, dosage compensation plays a crucial role in maintaining subunit stoichiometries. Indeed, we observed changes in the levels of a complex when its subunit stoichiometries were perturbed. We further analyzed compensation mechanisms using a proteasome-defective mutant as well as ribosome profiling, which provided strong evidence for compensation by ubiquitin-dependent degradation but not reduced translational efficiency. Thus, our study provides a systematic understanding of dosage compensation and highlights that this post-translational regulation is a critical aspect of robustness in cellular systems.

Impact of Spinopelvic sagittal alignment on the surgical outcomes of dropped head syndrome: a multi-center study.

BACKGROUND: Most of the previous studies about the surgical treatment of dropped head syndrome (DHS) are small case series, and their primary outcome measures were cervical alignment parameters. Therefore, little is known about the associations between pre- and postoperative global sagittal alignment in the whole spine and the clinical outcomes of the surgical treatment of DHS. In this study, we investigated the surgical outcomes of DHS, including correction of cervical and global spinal sagittal alignment. METHODS: This study was a retrospective observational study. Fifteen patients with DHS who had undergone correction surgery were enrolled. Surgical outcomes, including complications and implant failures, were investigated. We assessed cervical alignment parameters as well as spinopelvic global alignment parameters, including pelvic incidence (PI), lumbar lordosis (LL), and C7-sacral sagittal vertical axis (SVA). We examined the changes in these parameters using pre- and posoperative whole spine lateral radiographs. The parameters were compared between the failure and nonfailure groups. RESULTS: Recurrence of sagittal imbalance and horizontal gaze difficulty was observed in 6 cases (40%). In all, 3 cases (20%) exhibited a distal junctional failure and required multiple surgeries with extension of fusion. Of all the radiographic parameters compared between the failure and nonfailure groups, significant differences were only observed in pre and postoperative SVA and PI-LL. CONCLUSIONS: Our results suggest that the global sagittal alignment parameters, including PI-LL and SVA, were different between the patients with failure and non failure, and these parameters might have notable impacts on surgical outcomes. Surgeons should consider PI-LL and SVA while determining the surgical course for patients with DHS.

Lateral lumbar interbody fusion in revision surgery for restenosis after posterior decompression.

OBJECTIVE: The purpose of this study was to compare the clinical results of revision interbody fusion surgery between lateral lumbar interbody fusion (LLIF) and posterior lumbar interbody fusion (PLIF) or transforaminal lumbar interbody fusion (TLIF) with propensity score (PS) adjustments and to investigate the efficacy of indirect decompression with LLIF in previously decompressed segments on the basis of radiological assessment. METHODS: A retrospective study of patients who underwent revision surgery for recurrence of neurological symptoms after posterior decompression surgery was performed. Postoperative complications and operative factors were evaluated and compared between LLIF and PLIF/TLIF. Moreover, postoperative improvement in cross-sectional areas (CSAs) in the spinal canal and intervertebral foramen was evaluated in LLIF cases. RESULTS: A total of 56 patients (21 and 35 cases of LLIF and PLIF/TLIF, respectively) were included. In the univariate analysis, the LLIF group had significantly more endplate injuries (p = 0.03) and neurological deficits (p = 0.042), whereas the PLIF/TLIF group demonstrated significantly more dural tears (p < 0.001), surgical site infections (SSIs) (p = 0.02), and estimated blood loss (EBL) (p < 0.001). After PS adjustments, the LLIF group still showed significantly more endplate injuries (p = 0.03), and the PLIF/TLIF group demonstrated significantly more dural tears (p < 0.001), EBL (p < 0.001), and operating time (p = 0.04). The PLIF/TLIF group showed a trend toward a higher incidence of SSI (p = 0.10). There was no statistically significant difference regarding improvement in the Japanese Orthopaedic Association scores between the 2 surgical procedures (p = 0.77). The CSAs in the spinal canal and foramen were both significantly improved (p < 0.001). CONCLUSIONS: LLIF is a safe, effective, and less invasive procedure with acceptable complication rates for revision surgery for previously decompressed segments. Therefore, LLIF can be an alternative to PLIF/TLIF for restenosis after posterior decompression surgery.

Overview of dropped head syndrome (Combined survey report of three facilities).

BACKGROUND: Dropped head syndrome (DHS) is a low prevalence and the clinical features remain unclear. The purpose of the present study was to clarify the general overview of DHS. METHODS: The subjects were 67 consecutive DHS patients (17 men and 50 women; average age 72.9 ± 10.2 years) presenting difficulty of horizontal gaze in up-right position. The patients' background, global spinal alignment, clinical findings and treatment were analyzed. RESULTS: The peak population of DHS was 75-79-year-old females. The comorbidities included Parkinson's disease in 9 cases, minor trauma in 9 cases, post-cervical operation in 3 cases, mental depression in 3 cases, malignant tumor in 3 cases, diabetes mellitus in 2 cases and rheumatoid arthritis in 2 cases. The C2-C7 cervical coronal vertical axis was distributed more to the right side (2.6 ± 12.8 mm). Regarding sagittal alignment, 24 cases (35.8%) showed negative balanced DHS (N-DHS) and 43 cases (64.2%) showed positive balanced DHS (P-DHS). There were significant differences in C2-C7 angle, T1S, LL and PI-LL between the two groups. Cervical or back pain was present in 62 cases (92.5%), and average numerical rating scale was 3.0 ± 2.6. Fourteen cases (20.9%) recovered (average 11.3 months), but 29 cases (43.3%) did not recover without surgery. Twenty-four cases (35.8%) underwent surgery, 20 for cervical spine and 4 for thoraco-lumbar spine, and horizontal gaze difficulty was improved in all patients post-surgery. CONCLUSION: DHS was mainly observed in elderly women. About 20% of DHS patients recovered without surgical treatment. DHS was accompanied by scoliosis in 37.3% of the cases.

[Clinical features and diagnosis of lumbar fractures caused by pregnancy- and lactation-associated osteoporosis.]

Pregnancy- and lactation-associated osteoporosis is a rare disease. Although researchers have reported a few cases, there are no established diagnostic criteria for pregnancy- and lactation-associated osteoporosis. However, a diagnosis can be easily obtained by an accurate medical interview, physical examination, imaging studies, and laboratory data, including bone mineral density measurement. This disease should be suspected when a woman presents with severe back pain in the late stages of pregnancy or the early postpartum period. An accurate and prompt diagnosis helps with appropriate treatment and prevents the progression of the disease.

[Fracture management and current concepts related to pregnancy-associated osteoporosis.]

Pregnancy-associated osteoporosis is a rare condition characterized by a transient but significant reduction in bone mineral density. To date, the underlying pathophysiological mechanisms remain unclear. Related symptoms include severe back or hip pain secondary to vertebral fractures and/or transient osteoporosis of the hip, which typically occur during the third trimester or during lactation. Although most women are managed conservatively, a few women need surgery. Prompt diagnosis and appropriate treatment is important not only for pain control, but also to improve the woman's future quality of life.

Quadrant Analysis of Quantitative Computed Tomography Scans of the Femoral Neck Reveals Superior Region-Specific Weakness in Young and Middle-Aged Men With Type 1 Diabetes Mellitus.

We have previously shown that the intertrochanter of young and middle-aged patients with type 1 diabetes mellitus (T1DM) showed higher buckling ratio (an index of cortical instability) and lower volumetric bone mineral density (vBMD). However, we have not yet reported the detailed findings regarding the mechanical and density properties of the femoral neck. Therefore, we present a subanalysis of our previous study with the aim of further evaluating the middle third of the femoral neck via quadrant quantitative computed tomography in young and middle-aged patients with T1DM. Bone parameters in 4 anatomical quadrants (superoanterior [SA], inferoanterior [IA], inferoposterior [IP], and superoposterior [SP]) were cross-sectionally evaluated in 17 male T1DM patients and 18 sex-matched healthy controls aged between 18 and 49 yr using quadrant quantitative computed tomography analysis. Patients with T1DM had a thinner cortical thickness in the SP quadrant and a significantly lower cortical vBMD in the SA quadrant than the controls. The serum insulin-like growth factor-1 values in patients with T1DM were positively correlated with the average cortical thickness in the SA quadrant and the average trabecular vBMD in the SP quadrant of the femoral neck. The cortical thickness in controls was negatively correlated with age in the SP and IP quadrants. The cortical thickness in patients with T1DM showed no correlation with age in all quadrants. The fragility of the femoral neck was remarkable in the superior region of patients with T1DM. Insulin-like growth factor-1 may play an important role in superior cortical thinning and in lowering cortical vBMD. Furthermore, in young and middle-aged men with T1DM, the structure of the femoral neck exhibits similar changes as those observed with aging.

[New methods for the evaluation of bone quality. Relationship between bone resorption inhibitors and bony quality.]

Bone resorption inhibitors used in Japan are bisphosphonate, selective estrogen receptor modulators(SERMs), denosumab, eldecalcitol, and calcitonin. The structural and material properties of bone quality are important factors in osteoporosis treatment. In contrast to improvements in bone density, those in bone quality are difficult to clinically determine as no simple test is available and changes are difficult to detect. Numerous reports have been published on the mechanisms by which bone resorption inhibitors increase bone density and suppress bone fractures. This paper describes the effects of each bone resorption inhibitor and focusses on burr holes, trabeculae, microdamage, collagen cross-links, and microstructures.

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.

The potential effect of romosozumab on perioperative management for instrumentation surgery.

Background: Age-related changes in bone health increase the risk for complications in elderly patients undergoing orthopedic surgery. Osteoporosis is a key therapeutic target that needs to be addressed to ensure successful instrumentation surgery. The effectiveness of pharmacological interventions in orthopedic surgery, particularly the new drug romosozumab, is still unknown. We aim to evaluate the effect of 3-month romosozumab treatment on biomechanical parameters related to spinal instrumentation surgery, using the Quantitative Computed Tomography (QCT)-based Finite Element Method (FEM). Methods: This open-labeled, prospective study included 81 patients aged 60 to 90 years, who met the osteoporosis criteria and were scheduled for either romosozumab or eldecalcitol treatment. Patients were assessed using blood samples, dual-energy absorptiometry (DXA), and QCT. Biomechanical parameters were evaluated using FEM at baseline and 3 months post-treatment. The primary endpoints were biomechanical parameters at 3 months, while secondary endpoints included changes in regional volumetric bone mineral density around the pedicle (P-vBMD) and vertebral body (V-vBMD). Results: Romosozumab treatment led to significant gains in P-vBMD, and V-vBMD compared to eldecalcitol at 3 months. Notably, the romosozumab group showed greater improvements in all biomechanical parameters estimated by FEM at 3 months compared to the eldecalcitol group. Conclusion: Romosozumab significantly increased the regional vBMD as well as biomechanical parameters, potentially offering clinical benefits in reducing post-operative complications in patients with osteoporosis undergoing orthopedic instrumentation surgery. This study highlights the novel advantages of romosozumab treatment and advocates further research on its effectiveness in perioperative management.