An investigation of the differential therapeutic effects of romosozumab on postmenopausal osteoporosis patients with or without rheumatoid arthritis complications: a case-control study.

The impact of ROMO on the width of anabolic windows and the increase in BMD was reduced in the RA group compared to the non-RA group, and this reduction was associated with correlations to RA-related factors. PURPOSE: To investigate the effects of romosozumab (ROMO) in postmenopausal osteoporosis, with and without comorbid rheumatoid arthritis (RA). METHODS: In this retrospective, case-controlled, multicenter study, 171 postmenopausal patients who did not receive oral glucocorticoid, comprising 59 in the RA group and 121 in the non-RA group, received uninterrupted ROMO treatment for 12 months. Propensity score matching was employed to ensure comparability in clinical backgrounds, resulting in 41 patients in each group. Baseline characteristics were as follows: overall (mean age, 76.3 years; T-score of lumbar spine (LS), - 3.0; 45.1% were treatment-naive for osteoporosis); RA group (anti-cyclic citrullinated peptide antibody (ACPA) positivity, 80.5%; titer, 206.2 U/ml; clinical disease activity index (CDAI), 13.6; health assessment questionnaire disability index (HAQ-DI), 0.9). Bone mineral density (BMD) and serum bone turnover markers were monitored over a 12-month period. RESULTS: The rate of increase in the bone formation marker, PINP, and the rates of decrease in the bone resorption marker, TRACP-5b, exhibited a trend toward smaller changes in the RA group compared to the non-RA group, implying a smaller anabolic window. After 12 months, the RA group displayed lower BMD increases in the LS (9.1% vs. 12.6%; P = 0.013) and total hip (2.4% vs. 4.8%; P = 0.025) compared to the non-RA group. Multiple regression analysis in the all RA group (n = 59) for the association between RA-specific factors and 12-month BMD changes revealed negative correlations between ACPA titer and LS BMD and between HAQ-DI and femoral neck BMD. CONCLUSIONS: The efficacy of ROMO may be attenuated by RA-related factors.

Characteristics in patients with very early therapeutic response of condoliase chemonucleolysis for lumbar disc herniation.

INTRODUCTION: Treatment of lumbar disc herniation (LDH) using condoliase chemonucleolysis (CC) requires more time than surgery to demonstrate therapeutic effects. This study aimed to identify patients who show significant improvement in leg pain very early after CC and to determine pretreatment factors that can predict a very early therapeutic response. METHODS: The study included 52 patients who underwent CC for treatment-resistant LDH. Scores for low back and leg pain measured by a numerical rating scale were assessed at four time points (1 day, 1 week, 1 month, and 3 months after CC). Patients who reported subjective pain relief the day after treatment and further exhibited an improved straight leg raising (SLR) angle compared to pretreatment were classified as "very early responders (VER)". RESULTS: Of the 52 patients, 39 (75%) were VER, and 13 (25%) were non-VER. The VER showed earlier improvement in leg pain. The VER had a significantly higher proportion of positive SLR test patients (p = 0.01) and a significantly smaller pretreatment SLR angle compared to the non-VER (VER vs. non-VER: 40.6 ± 19.0 vs. 63.1 ± 16.9, p < 0.001). There were no significant differences in the level, type, and size of LDH and the disc regression rate between the two groups. CONCLUSIONS: Patients with a smaller pretreatment SLR angle are more likely to experience very early or early symptomatic relief, with a significant and sustained reduction in leg pain up to 3 months after CC treatment.

Baseline serum PINP level is associated with the increase in hip bone mineral density seen with Romosozumab treatment in previously untreated women with osteoporosis.

Baseline serum PINP value was significantly and independently associated with the increased bone mineral density (≥ 3%) in both total hip and femoral necks by 12 months of romosozumab treatment in patients with treatment-naive postmenopausal osteoporosis. PURPOSE: Some patients fail to obtain a sufficiently increased hip bone mineral density (BMD) by romosozumab (ROMO) treatment. This study aimed to investigate the prognostic factor for increased hip BMD with ROMO in patients with treatment-naive postmenopausal osteoporosis. METHODS: This prospective, observational, and multicenter study included patients (n = 63: mean age, 72.6 years; T-scores of the lumbar spine [LS], - 3.3; total hip [TH], - 2.6; femoral neck [FN], - 3.3; serum type I procollagen N-terminal propeptide [PINP], 68.5 µg/L) treated by ROMO for 12 months. BMD and serum bone turnover markers were evaluated at each time point. A responder analysis was performed to assess the patient percentage, and both univariate and multivariate analyses were performed to investigate the factors associated with clinically significant increased BMD (≥ 3%) in both TH and FN. RESULTS: Percentage changes of BMD from baseline in the LS, TH, and FN areas were 17.5%, 4.9%, and 4.3%, respectively. In LS, 96.8% of patients achieved ≥ 6% increased LS-BMD, although 57.1% could not achieve ≥ 3% increased BMD in either TH or FN. Multiple regression analysis revealed that only the baseline PINP value was significantly and independently associated with ≥ 3% increased BMD in both TH and FN (p = 0.019, 95% confidence interval = 1.006-1.054). The optimal cut-off PINP value was 53.7 µg/L with 54.3% sensitivity and 92.3% specificity (area under the curve = 0.752). CONCLUSIONS: In a real-world setting, baseline PINP value was associated with the increased BMD of TH and FN by ROMO treatment in treatment-naive patients.

Assessment of bone health in patients with prostate cancer using cancer staging computed tomography.

PURPOSE: To evaluate the utility of vertebral Hounsfield unit (HU) values from computed tomography (CT) in cancer staging as a supplementary screening tool for bone health among prostate cancer (PCa) patients. METHODS: T-scores of bone mineral density (BMD) in each lumbar vertebra (L1-L4) and hip for newly diagnosed PCa patients (N = 139) were measured using dual-energy X-ray absorptiometry (DXA). The degenerative changes in each lumbar vertebra were assessed, and the HU values of trabecular bone in axial CT images of each vertebral body (vertebral CT-HU value) were measured using staging CT. RESULTS: 556 vertebrae were analyzed. 326 of 556 (59%) lumbar vertebrae had degenerative changes. The vertebral CT-HU value was positively correlated with the lumbar BMD T-score, with higher correlation coefficients observed in vertebrae without degenerative changes (r = 0.655, N = 230) when compared to vertebrae with degenerative changes (r = 0.575, N = 326). The thresholds matching BMD T-scores of - 2.0 and - 1.5 set by cancer treatment-induced bone loss guidelines were 95 HU and 105 HU, respectively. Based on the intervention threshold (lumbar BMD T-score < - 1.5), 15.1% of PCa patients required osteoporosis treatment; and, this value increased to 30.9% when L1-L4 CT-HU thresholds that corresponded to BMD T-score < - 1.5 were used. CONCLUSION: Lumbar BMD values from DXA may not reflect true bone health in PCa patients who often have lumbar degenerative diseases. Thresholds based on the vertebral CT-HU value can be used as a supplementary method to identify PCa patients who need anti-osteoporosis drugs.

Effects of follow-on therapy after denosumab discontinuation in patients with postmenopausal osteoporosis.

OBJECTIVES: To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation. METHODS: In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (n = 26) or teriparatide (TPTD) (n = 27) were switched to DMAb (administered 2.6 times), and then discontinued. Patients (73.1 years, T-scores of the lumbar spine [LS] - 2.7 and femoral neck [FN] - 2.2) were switched to either (1) raloxifene (RAL) (n = 13) or BP [(2) weekly or monthly BP (wmBP) (n = 29) or (3) zoledronate (ZOL) (n = 11)], based on each physician's decision (mean interval after final DMAb administration was 7.2 months). Bone mineral density (BMD) at final DMAb administration were set as baseline. RESULTS: Changes in LS BMD at 1.5 years after final DMAb administration were -2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (p = .31 between groups), and in FN BMD were -3.8%, -0.8%, and 1.8%, respectively (p = .02 between the RAL and ZOL; p = .048 between the RAL and BP). Clinical vertebral fracture incidence during 1.5 years after final DMAb administration was 23.1% in the RAL, 3.4% in the wmBP, and 0.0% in the ZOL (p = .048 between the RAL and ZOL; p = .015 between the RAL and BP). No significant differences were observed in these parameters between the wmBP and ZOL. CONCLUSION: These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required.

Comparison in the same intervertebral space between titanium-coated and uncoated PEEK cages in lumbar interbody fusion surgery.

BACKGROUNDS: Disadvantages of polyetheretherketone (PEEK) cages are their smooth and hydrophobic surfaces and their lack of osteoconductivity. Titanium (Ti) coated PEEK cage has been innovated to overcome these potential concerns. However, few well-designed studies have investigated the efficacy of Ti-coated PEEK cage on interbody fusion in humans. This study aimed to evaluate the efficacy of Ti coating on bone ongrowth at bone-implant surface by simultaneously comparing Ti-coated and uncoated PEEK cages in the same intervertebral space. METHODS: This study is a prospective comparative study for the two different cages. Twenty-six subjects who underwent one-level instrumented posterior lumbar interbody fusion (PLIF) were included. Two PEEK cages [a plasma-sprayed Ti-coated (PTC-PEEK) and an uncoated PEEK cage] were inserted in the same intervertebral space. Fusion rates, cage subsidence, and vertebral cancellous condensation (VCC) around the cage, which indicates bone growth on the surface of each cage, were assessed by thin-slice computed tomography (CT) immediately (within 1 week) and at 3 months postoperatively. A functional radiograph was obtained at 3 and 12 months postoperatively. RESULTS: Twenty-three subjects showed solid fusion at 3 months postoperatively (fusion rate, 88%). Cage subsidence was not observed. VCC was often observed around the PTC-PEEK cage as evaluated by completely synchronized CT images between immediately and at 3 months postoperatively. Quantified VCC around the cage was significantly larger in the PTC-PEEK cage than in the uncoated PEEK cage (P = 0.01). CONCLUSIONS: The Ti-coated PEEK cage exhibits radiographic signs, suggesting bone ongrowth, as represented by VCC around the cage compared with that around the uncoated PEEK cage. The Ti-coated PEEK cage has the potential to promote solid fusion and to improve clinical outcomes in lumbar interbody fusion surgery.

Development of scoliosis in young children with osteogenesis imperfecta undergoing intravenous bisphosphonate therapy.

The purpose of this study was to clarify the prevalence of scoliosis and determine risk factors for the development of scoliosis in young children with osteogenesis imperfecta (OI) who underwent intravenous pamidronate (PAM) therapy. Thirty-four young children with OI who had no scoliosis at the first PAM administration underwent cyclic PAM therapy alone. The medical records and radiographs of these patients were retrospectively reviewed. We examined the relationship between scoliosis (Cobb angle ≥ 10) and type of OI (Sillence classification: types I, III, and IV), physical mobility, Z-scores of bone mineral density in L2-4 of the lumbar spine (L2-4 BMD Z-scores), age of patients at first treatment with PAM, pelvic frontal tilt and leg-length discrepancy. The prevalence of scoliosis was 23.5% in 34 young children with OI who underwent PAM therapy for a mean of 4.2 years. Lower L2-4 BMD Z-scores, the presence of coronal and sagittal vertebral deformities and higher percentage of corrective osteotomy in the lower extremities were significant risk factors for the development of scoliosis. In patients with type III or IV OI, L2-4 BMD Z-scores were significantly lower (p = 0.02) and the percentage of patients who started PAM therapy in early childhood was significantly lower in scoliosis group than in the non-scoliosis group (p = 0.01). Development of scoliosis depends on the severity of OI and has a strong relationship with bone fragility even under PAM therapy. Starting intravenous PAM therapy in infancy or early childhood has a potential to prevent the occurrence and progression of scoliosis associated with bone fragility in young children with severe type III or IV OI.

Assessment of the effects of switching oral bisphosphonates to denosumab or daily teriparatide in patients with rheumatoid arthritis.

The aim of this observational, non-randomized study was to clarify the unknown effects of switching oral bisphosphonates (BPs) to denosumab (DMAb) or daily teriparatide (TPTD) in patients with rheumatoid arthritis (RA). The characteristics of the 194 female patients included in the study were 183 postmenopausal, age 65.9 years, lumbar spine (LS) T score -1.8, femoral neck (FN) T score -2.3, dose and rate of taking oral prednisolone (3.6 mg/day) 75.8%, and prior BP treatment duration 40.0 months. The patients were allocated to (1) the BP-continue group (n = 80), (2) the switch-to-DMAb group (n = 74), or (3) the switch-to-TPTD group (n = 40). After 18 months, the increase in bone mineral density (BMD) was significantly greater in the switch-to-DMAb group than in the BP-continue group (LS 5.2 vs 2.3%, P < 0.01; FN 3.8 vs 0.0%, P < 0.01) and in the switch-to-TPTD group than in the BP-continue group (LS 9.0 vs 2.3%, P < 0.001; FN 4.9 vs 0.0%, P < 0.01). Moreover, the switch-to-TPTD group showed a higher LS BMD (P < 0.05) and trabecular bone score (TBS) (2.1 vs -0.7%; P < 0.05) increase than the switch-to-DMAb group. Clinical fracture incidence during this period was 8.8% in the BP-continue group, 4.1% in the switch-to-DMAb group, and 2.5% in the switch-to-TPTD group. Both the switch-to-DMAb group and the switch-to-TPTD group showed significant increases in LS and FN BMD, and the switch-to-TPTD group showed a higher increase in TBS compared to the BP-continue group at 18 months. Switching BPs to DMAb or TPTD in female RA may provide some useful osteoporosis treatment options.

The effects of switching daily teriparatide to oral bisphosphonates or denosumab in patients with primary osteoporosis.

The aim of this 12-month, observational study was to compare the effects of switching daily teriparatide (TPTD) to oral bisphosphonates (BP) therapy or denosumab (DMAb) therapy in patients with primary osteoporosis. Patients [n = 78; 71 postmenopausal women and seven men; mean age 76.3 (64-94) years; mean duration of prior daily TPTD therapy 20.1 (6-24) months] were allocated to either the (1) "switch-to-BP" group [n = 36; weekly alendronate 35 mg (n = 19), weekly risedronate 17.5 mg (n = 12), monthly minodronate 50 mg (n = 5)]; or (2) "switch-to-DMAb" group (n = 42; 60 mg sc every 6 months) based on each physicians' decision. Changes in bone mineral density (BMD) and serum bone turnover markers were monitored every 6 months. No significant difference was observed in baseline clinical characteristics between the groups. After 12 months, the increase in BMD was significantly greater in the switch-to-DMAb group compared to the switch-to-BP group: lumbar spine (6.2 vs. 2.6 %; P < 0.01), total hip (4.2 vs. 1.1 %; P < 0.05), and femoral neck (3.5 vs. 1.4 %; P < 0.05). In addition, the patients in the switch-to-DMAb group showed a significant decrease compared to those in the switch-to-BP group in TRACP-5b (-55.8 vs. -32.8 %; P < 0.01) and ucOC (-85.5 vs. -65.0 %; P < 0.001), while no significant difference was observed in PINP (-67.5 vs. -62.1 %). Switching daily TPTD to DMAb significantly increased BMD and decreased bone resorption marker compared to switching to oral BP at 12 months, and thus may provide an effective sequential treatment option after daily TPTD treatment.

Comparison of the effects of denosumab between a native vitamin D combination and an active vitamin D combination in patients with postmenopausal osteoporosis.

The aim of this 12-month, retrospective study was to compare the effects of denosumab (DMAb; 60 mg subcutaneously every 6 months) plus native vitamin D (VD) (cholecalciferol) combination therapy with DMAb plus active VD analog (alfacalcidol) combination therapy in patients with postmenopausal osteoporosis. Patients [N = 127; mean age 75.6 years (range 58-93 years); 28 treatment-naïve patients, 59 patients treated with oral bisphosphonate therapy, 40 patients treated with teriparatide daily] were allocated to either (1) the DMAb plus native VD group (n = 60; cholecalciferol, 10 µg, plus calcium, 610 mg/day; 13 treatment-naïve patients, 28 patients treated with oral bisphosphonate therapy, and 19 patients treated with teriparatide daily) or (2) the DMAb plus active VD group [n = 67; alfacalcidol, 0.8 ± 0.0 µg, plus calcium, 99.2 ± 8.5 mg/day; 15 treatment-naïve patients, 31 patients treated with oral bisphosphonate therapy, and 21 patients treated with teriparatide daily) on the basis of each physician's decision. Changes in bone mineral density (BMD), serum bone turnover marker levels, and fracture incidence were monitored every 6 months. There were no significant differences in baseline age, BMD, bone turnover marker levels, and prior treatments between the two groups. After 12 months, compared with the DMAb plus native VD group, the DMAb plus active VD group showed similar increases in the BMD of the lumbar spine (6.4% vs 6.5%) and total hip (3.3% vs 3.4%), but significantly greater increases in the BMD of the femoral neck (1.0% vs 4.9%, P < 0.001) and the distal part of the forearm (third of radius) (-0.8% vs 3.9%, P < 0.01). These tendencies were similar regardless of the differences in the prior treatments. The rates of decrease of bone turnover marker levels were similar for tartrate-resistant acid phosphatase isoform 5b (-49.0% vs -49.0%), procollagen type I N-terminal propeptide (-45.9% vs -49.3%), and undercarboxylated osteocalcin (-56.0  vs -66.5%), whereas serum intact parathyroid hormone levels were significantly lower in the DMAb plus active VD group (47.6 pg/mL vs 30.4 pg/mL, P < 0.001). The rate of hypocalcemia was 1.7% in the DMAb plus native VD group and 1.5% in the DMAb plus active VD group, and the rate of clinical fracture incidence was 8.3% in the DMAb plus native VD group and 4.5% in the DMAb plus active VD group, with no significant difference between the groups. DMAb with active VD combination therapy may be a more effective treatment option than DMAb with native VD combination therapy in terms of increasing BMD of the femoral neck and distal part of the forearm and also maintaining serum intact parathyroid hormone at lower levels.

Differences in vertebral morphology around the apical vertebrae between neuromuscular scoliosis and idiopathic scoliosis in skeletally immature patients: a three-dimensional morphometric analysis.

BACKGROUND: Recent morphological analyses of vertebrae in patients with scoliosis have revealed three-dimensional (3D) deformities in the vertebral bodies. However, it remains controversial whether these deformities are secondary changes caused by asymmetrical vertebral loading or primary changes caused by aberrant asymmetrical vertebral growth. Furthermore, the difference in vertebral morphology between scoliosis with different pathogeneses remains unclear. This study was aimed to investigate the difference in the coronal asymmetry of vertebral bodies between neuromuscular scoliosis (NS) in Duchenne muscular dystrophy (DMD) and idiopathic scoliosis (IS) using in vivo 3D analysis. METHODS: Twelve male skeletally immature patients with NS in DMD and 13 female skeletally immature patients with IS who underwent corrective fusion at our institution were included retrospectively. 3D bone models of the apical and adjacent upper and lower vertebrae in the major curve in the NS patients and in the main and compensatory curves in the IS patients were constructed using an image processing workstation. The heights of the concave and convex sides of the vertebral bodies were measured at the anterior, middle, and posterior and the concave-to-convex vertebral height ratios (VHR) were calculated. RESULTS: The mean VHRs (anterior/middle/posterior) for the main curve for IS (0.897 ± 0.072/0.832 ± 0.086/0.883 ± 0.059) were significantly smaller than those for NS (0.970 ± 0.048/0.934 ± 0.081/0.958 ± 0.043) in all three parts (p < 0.001). Those of the compensatory curve in IS (0.968 ± 0.045/0.942 ± 0.067/0.967 ± 0.046) did not differ significantly from the NS values in any part. CONCLUSIONS: When compared to the wedging of the vertebral bodies around apical vertebrae in the major curve in NS, which was caused by asymmetric loading, the wedge deformities in both the main and compensatory curves in IS were more severe than would be expected. Our results indicated that morphometric characteristics of vertebral bodies differed according to the pathogenesis of scoliosis and that the pathology of the wedging of vertebral bodies in IS could not be a result only of asymmetric loading to the vertebral bodies.

Circulating sclerostin and dickkopf-1 levels in ossification of the posterior longitudinal ligament of the spine.

Sclerostin and dickkopf-1(DKK1) are Wnt/ß-catenin signal antagonists that play an important role in bone formation. Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by pathological ectopic ossification of the posterior longitudinal ligament and ankylosing spinal hyperostosis. The aims of this study were to evaluate serum sclerostin and DKK1 levels in persons with OPLL and to identify its relationship with bone metabolism and bone mass in persons with OPLL. This was a case-control study, and 78 patients with OPLL were compared with 39 age- and sex-matched volunteers without OPLL. We analyzed the relationship with calciotropic hormones, bone turnover markers, OPLL localization, number of ossified vertebrae, and bone mineral density of total hip (TH-BMD). Serum sclerostin levels in men with OPLL were significantly higher than in men in the control group (control group: mean = 45.3 pmol/L; OPLL group: mean = 75.7 pmol/L; P = 0.002). Age and sclerostin levels were positively correlated in men with OPLL (r = 0.43; P = 0.002). Serum sclerostin levels in men with OPLL had a positive correlation with TH-BMD Z-score (r = 0.511; P = 0.011, n = 30). There was a strong negative correlation between serum sclerostin levels and serum DKK1 levels in men with OPLL (r = -0.506; P < 0.001). Bone and mineral metabolism in OPLL differs between men and women. In men with OPLL, systemic secretion of sclerostin increases with advancing age and with higher bone mass. These two Wnt/ß-catenin signal antagonists have the opposite effect in persons with OPLL, and higher serum sclerostin levels are counterbalanced by underproduction of DKK1.

Factors affecting postoperative activities of daily living in patients with osteoporotic vertebral collapse with neurological deficits.

Surgical treatment of osteoporotic vertebral collapse (OVC) with neurological deficits presents significant clinical challenges because some patients have fragile bones and often have medical comorbidities, which affect the severity of osteoporosis. We hypothesized that clinical results of surgery in these patients depend on the extent of medical comorbidities that induce secondary osteoporosis. The aim of this study is to examine the effects of medical history and comorbidities on surgical outcomes for these patients, along with the factors that predict postoperative function in activities of daily living (ADL). We retrospectively reviewed data for 88 patients with OVC and neurological deficits who underwent surgery. We assessed clinical results regarding neurological deficits and function in ADL. The presence or absence of comorbidities responsible for secondary osteoporosis and treatments or medical events that affect bone metabolism were examined. We performed statistical analysis to examine prognostic factors for postoperative function in ADL. Of 88 patients, the distributions of comorbidities, treatment, and events in medical history were as follows: hypertension, 57 patients (64.8%); chronic kidney disease (CKD) stage 3 or 4, 32 (36.4%); diabetes mellitus, 16 (18.2%); liver dysfunction, 11 (12.5%); cardiovascular disease, 10 (11.4%); rheumatoid arthritis, 9 (10.2%); and glucocorticoid intake, 8 (9.1%). Twenty-five patients (28.4%) represented poor postoperative ADL (chair-bound or bed-bound), and 11 of 25 patients with poor postoperative ADL represented full neurological recovery. Multivariate analysis revealed decreased estimated glomerular filtration rate (odds ratio 0.96; 95% confidence interval 0.93-0.99; p = 0.005) and a high serum alkaline phosphatase (ALP) level (odds ratio 1.01; 95% CI 1.00-1.02; p = 0.01) were strong predictive factors for poor postoperative function in ADL. The majority of patients with poor postoperative function in ADL had advanced CKD with a disorder of bone metabolism as well as bone fragility.

3D morphometric analysis of laminae and facet joints in patients with degenerative spondylolisthesis.

OBJECTIVE: To clarify the three-dimensional (3D) morphometric characteristics of the spine in patients with degenerative spondylolisthesis (DS). METHODS: 3D morphometric analyses of laminae and facets were performed and compared for a DS group, an age-matched spinal canal stenosis (LCS) group, and a control group of young persons without spinal disease. 3D facet sagittal angles (3D-FSAs), 3D facet axial angle (3D-FAAs), and 3D-FAA tropism at L3 and at L4 were measured by extracting the 3D inferior articular process. The 3D lamina inclination angles (3D-LIAs) of L3 and L4 were also measured by extracting the ventral surface of the laminae. RESULTS: The 3D-FSAs at L4 in the DS group were significantly higher than for the other groups, but the difference in 3D-FSAs at L3 was not statistically significant among the groups. The 3D-FAAs at L4 in the DS group were significantly lower than in the control group. There was no significant difference in other factors. CONCLUSIONS: 3D morphometric analysis clarified that DS is significantly correlated with horizontalization (higher 3D-FSA), but is not correlated with sagittalization (lower 3D-FAA) and tropism (3D-FAA tropism) of facet joints or horizontalization of laminae (3D-LIA). There were no morphometric characteristics at the cranial adjacent segment of DS.

Surgical treatment for osteoporotic vertebral collapse with neurological deficits: retrospective comparative study of three procedures--anterior surgery versus posterior spinal shorting osteotomy versus posterior spinal fusion using vertebroplasty.

PURPOSE: In general, osteoporotic vertebral collapse (OVC) with neurological deficits requires sufficient decompression of neural tissues to restore function level in activities of daily living (ADL). However, it remains unclear as to which procedure provides better neurological recovery. The primary purpose of this study was to compare neurological recovery among three typical procedures for OVC with neurological deficits. Secondary purpose was to compare postoperative ADL function. METHODS: We retrospectively reviewed data for 88 patients (29 men and 59 women) with OVC and neurological deficits who underwent surgery. Three typical kinds of surgical procedures with different decompression methods were used: (1) anterior direct neural decompression and reconstruction (AR group: 27 patients), (2) posterior spinal shorting osteotomy with direct neural decompression (PS group: 36 patients), and (3) posterior indirect neural decompression and short-segment spinal fusion combined with vertebroplasty (VP group: 25 patients). We examined clinical results regarding neurological deficits and function level in ADL and radiological results. RESULTS: The mean improvement rates for neurological deficits and ADL function level were 60.1 and 55.0%, respectively. There were no significant differences among three groups in improvement rates for neurological deficits or ADL function level. The VP group had a significantly lower estimated mean blood loss (338 mL) and mean duration of surgery (229 min) than both the AR and PS groups (p < 0.001). CONCLUSION: Direct neural decompression is not always necessary, and the majority of patients can be treated with a less-invasive procedure such as short-segment posterior spinal fusion with indirect decompression combined with vertebroplasty. The high-priority issue is careful evaluation of patients' general health and osteoporosis severity, so that the surgeon can choose the procedure best suited for each patient.

Preoperative Risk Factors Affecting Outcome in Surgically Treated Pyogenic Spondylodiscitis.

STUDY DESIGN: Retrospective study. OBJECTIVE: The primary aim of this study was to investigate the predictors of severe complications in patients following surgery for pyogenic spondylodiscitis (PS) using a surgeon-maintained database. The secondary aim was to investigate the predictors of early recovery. METHODS: We introduced a surgeon-maintained database of prospectively collected multicenter data that mainly focused on perioperative complications in 2012. Our surgeon-maintained database allows the retrospective collection of detailed data. We analyzed 143 patients who underwent surgery for PS from the 19,056 patients in the prospective surgeon-maintained database at 27 affiliated institutions between 2013 and 2017. Data relating to preoperative patient factors, infection factors, surgical factors, and pre- and postoperative blood tests was retrospectively collected. We performed multivariate regression analysis to evaluate the predictors of postoperative severe complications and early recovery in patients with PS. RESULTS: High updated Charlson comorbidity index (uCCI), chronic pulmonary disease, diabetes, Gram-negative bacteria, pyogenic osteoarthritis, high preoperative white blood cell count, and low preoperative platelet count were significantly associated with severe complications in patients undergoing surgery for PS. A high uCCI was the sole independent negative predictor on early recovery. CONCLUSION: Careful perioperative management is necessary if surgery is performed on patients who are at a high risk of life-threatening events.

Genetic insights into ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.

Development of Atypical Ulnar Fracture is Associated with Bisphosphonate Therapy and Severe Spinal Deformity: A Case Report.

Atypical ulna fracture (AUF) is relatively rare and is known to be associated with prolonged bisphosphonate (BP) use. The developmental mechanism remains unclear. We report a patient with an AUF associated with BP and severe spinal deformity. The patient was an 85-year-old woman receiving oral alendronate for 8 years without vitamin D supplementation. During regular kitchen work, she needed left upper limb support. She presented with atraumatic pain over the ulna. Radiographs revealed a transverse fracture in the proximal ulna and ulna bowing deformity. Whole-spine standing radiographs showed severe degenerative kyphoscoliosis. The skin induration with pigmentation on her left elbow that suggested prolonged overload and during standing work, coincided exactly with fracture location. This report suggests that 'direct stress', with persistent local overload on the proximal ulna, is one of the developmental mechanisms of AUF, in addition to persistent suppression of bone remodelling by prolonged BP use and vitamin D deficiency. Level of Evidence: Level V (Therapeutic).

Tolerability of the first infusion of once-yearly zoledronic acid within one to two weeks after hip fracture surgery.

OBJECTIVE: Once-yearly infusions of zoledronic acid (ZA) 5 mg may be optimal for secondary fracture prevention after hip fracture (HF), but there are crucial side effects of ZA. This study assessed the tolerability of the first infusion of once-yearly ZA within one to two weeks after HF surgery and to identify risk factors for acute-phase reactions (APRs) and the decrease in serum calcium (Ca) concentration. METHODS: We analyzed 84 patients (average age: 83 years, 18 men and 66 women) who met the inclusion criteria. The patients underwent the first infusion of ZA one to two weeks after HF surgery and received antipyretic analgesics and active vitamin D analog. RESULTS: APRs occurred in ten patients (11.9%) and all these patients had pyrexia (>37.5 °C) and/or other symptoms. The asymptomatic hypocalcemia (serum Ca < 8.3 mg/dL) incidence was 6.0% at 7 days after ZA infusion. Compared with female patients without APRs, female patients with APRs had significantly higher levels of serum 25-dihydroxyvitamin D at baseline and serum C-reactive protein on the day ZA was administered (day 0). Multiple linear regression analyses showed that serum level of tartrate-resistant acid phosphatase-5b were significantly associated with an absolute decrease in serum corrected Ca from day 0 to day 7. CONCLUSIONS: The first infusion of ZA within one to two weeks after HF surgery was well tolerated with the combined use of antipyretic analgesics and active vitamin D analog. Higher inflammatory condition after surgery which is more likely sensitized by ZA administration may increase the risk of APRs, and high bone turnover may increase hypocalcemia risk.