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.

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.

Low serum albumin concentration is associated with increased risk of osteoporosis in postmenopausal patients with rheumatoid arthritis.

BACKGROUND: The risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA. METHODS: This study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, -1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ -2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism. RESULTS: In non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p < 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58. CONCLUSIONS: Low serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis.

OBJECTIVES: To investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis. METHODS: In this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n=50) or patients previously treated with bisphosphonates (BP; n=37) or denosumab (DMAb; n=45) or teriparatide (TPTD; n=16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] -3.2 and total hip [TH] -2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months. RESULTS: At 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P<0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P<0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; µg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r=-2.8, P<0.001) and value of PINP at 1 month (r=0.04, P<0.01) for LS, and difference of prior treatment (r=-1.3, P<0.05) and percentage change of TRACP-5b at 1 month (r=-0.06, P<0.05) for TH. CONCLUSIONS: The early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.

Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis.

PURPOSE: To investigate the effects of prior treatment and the predictors of early treatment response to romosozumab (ROMO) in patients with postmenopausal osteoporosis. METHODS: In this prospective, observational, multicenter study, 130 treatment-naïve patients (Naïve; n = 37) or patients previously treated with bisphosphonates (BP; n = 33), denosumab (DMAb; n = 45), or teriparatide (TPTD; n = 15) (age, 75.0 years; T-scores of the lumbar spine [LS] -3.2 and femoral neck [FN] -2.9) were switched to ROMO based on their physician's decision. Bone mineral density (BMD) and serum bone turnover markers were evaluated for six months. RESULTS: At six months, LS BMD changes were 13.6%, 7.5%, 3.6%, and 8.7% (P < .001 between groups) and FN BMD changes were 4.2%, 0.4%, 1.6%, and 1.5% (P = .16 between groups) for Naïve, BP, DMAb, and TPTD groups, respectively. Changes in N-terminal type I procollagen propeptide (PINP; µg/L) levels from baseline â†’ one month were 72.7 â†’ 139.0, 33.5 â†’ 85.4, 30.4 â†’ 54.3, and 98.4 â†’ 107.4, and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) (mU/dL) were 474.7 â†’ 270.2, 277.3 â†’ 203.7, 220.3 â†’ 242.0, and 454.1 â†’ 313.0 for Naïve, BP, DMAb, and TPTD groups, respectively. Multivariate regression analysis revealed that significant predictors of LS BMD change at six months were prior treatment difference (r = -3.1, P = .0027) and TRACP-5b percentage change (r = -2.8, P = .0071) and PINP value at one month (r = 3.2, P = .0021). CONCLUSION: Early effects of ROMO on the increase in LS BMD are significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers. MINI ABSTRACT: Early effects of ROMO on the increase in LS BMD at six months is significantly affected by the difference of prior treatment and also predicted by the early change of bone turnover markers in patients with postmenopausal osteoporosis.

The efficacy and safety of additional administration of tacrolimus in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab.

OBJECTIVES: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown. METHODS: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] ≥ 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study. RESULTS: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p < 0.001), CDAI from 17.7 to 7.6 (p < 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p < 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≤2.7 or CDAI ≤10) at week 24. CONCLUSIONS: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.

Ramsay hunt syndrome in a patient with rheumatoid arthritis after treatment with infliximab.

A 39-year-old female patient with rheumatoid arthritis developed Ramsay Hunt syndrome after infliximab treatment. This condition is caused by the reactivation of varicella zoster virus infection in the geniculate ganglion of facial nerve in the host's immunosuppression. She was treated immediately with valaciclovir and hydrocortisone, and the complete recovery was achieved at 6 months after the onset. This is the first report of Ramsay Hunt syndrome as an adverse effect of infliximab in rheumatoid arthritis.

Development of leaky-wave antenna for digitally controlled millimeter-wave interferometer.

We propose a new interferometer concept that can realize electron-density distribution measurement with high spatial and moderate temporal resolution. The image non-radiative dielectric guide antenna can probe a wide measurement area simultaneously. We fabricated the antenna with an electromagnetic simulator and confirmed that the simulated and measured radiation patterns are consistent with each other. In addition, we found that the antenna shows the required characteristics such as scanning characteristics, which depend on the input frequency.

Reconstruction of edge density profiles on Large Helical Device using ultrashort-pulse reflectometry.

Reflectometry has been expected to be one of the key diagnostics to measure density profiles. We have applied an ultrashort-pulse reflectometry (USPR) system to Large Helical Device in the National Institute for Fusion Science. Wide frequency band system is required to obtain wide density profile since an incident wave is reflected at the density layer corresponding to its cutoff frequency. The reflectometry utilizes an impulse with less than 30 ps pulse width as a source. Since the bandwidth of an impulse has an inverse relation to the pulse width, we can cover the frequency range of micro- to millimeter waves (18-40 GHz) with a single source. The density profiles can be reconstructed by collecting time-of-flight (TOF) signals for each frequency component of an impulse reflected from the corresponding cutoff layer. We utilize the signal record analysis (SRA) method to reconstruct the density profiles from the TOF signal. The effectiveness of the SRA method for the profile reconstruction is confirmed by a simulation study of the USPR using a finite-difference time domain method.

Development of multichannel intermediate frequency system for electron cyclotron emission radiometer on KSTAR Tokamak.

Plasma experiments on KSTAR are scheduled to start up this year (2008). We have developed an electron cyclotron emission (ECE) radiometer to measure the radial electron temperature profiles in KSTAR experiments. The radiometer system consists, briefly, of two downconversion stages, amplifiers, bandpass filter banks, and video detectors. These components are made commercially or developed in house. The system detects ECE power in the frequency range from 110 to 196 GHz, the detected signal being resolved by means of 48 frequency windows. Before installation of this system on KSTAR, we installed a part of this system on large helical device (LHD) to study the system under similar plasma conditions. In this experiment, the signal amplitude, considered to be proportional to the electron temperature, is measured. The time-dependent traces of the electron temperature measured by this radiometer are in good agreement with those provided by the LHD Michelson spectrometer. The system noise level which limits the minimum measurable temperature (converted to the electron temperature) is about 30 eV.