scholarly journals SAT0474 WHAT DETERMINES THE EFFECT OF THERAPY WITH DENOSUMAB ON BONE IN WOMEN WITH RHEUMATOID ARTHRITIS AND OSTEOPOROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1194.1-1194
Author(s):  
P. Kovalenko ◽  
I. Dydykina ◽  
A. Smirnov ◽  
E. Nasonov

Background:RANK-ligand is essential for osteoclast development, activation, and survival and it is a key mediator of increased osteoclast activity in rheumatoid arthritis (RA). Denosumab is a monoclonal antibody that binds RANK-ligand.Objectives:The aim of this study was to evaluate the effects of denosumab on bone mineral density (BMD) and to define a contribution of factors: anamnesis, clinical/laboratory markers, glucocorticoids (GC) intake, etc. on the response to therapy with denosumab in women with RA and osteoporosis (OP).Methods:66 postmenopausal women (mean age 59,6±7,4) with RA (mean duration 17,7±10,4 years) and OP received s/c denosumab 60 mg every 6 months pro 12 months. RF-positive were 72%, ACCP – 74% of patients. 34 (49%) patients continued GC. At baseline and after 12 months it was carried out the dual energy x-ray absorptiometry at 3 sites: lumbar spine (L1-L4), hip neck (HN) and distal forearm (DF) and x-ray of hands and feet (Sharp/van der Heijde (SVH) score). The Statistica 6.0 was used.Results:After therapy it was noted the increase (р < 0,05) of BMD in L1-L4 and HN, a tendency to increase (р =0,0529) in DF. Mean BMD (L1-L4) before\after the treatment was 0,821 ± 0,104 g/cm2vs 0,864 ± 0,110 g/cm2, at HN was 0,625 ± 0,089 g/сm2vs 0,639 ± 0,088 g/сm2, at DF was 0,498 ± 0,090 g/сm2vs 0,503 ± 0,089 g/сm2. The mean change of BMD (%) after 12 months at L1-L4 was +4,6%, at HN +2,8%, at DF +0,7%. Positive response (increase or stabilization of BMD) was noted in 89% patients at L1-L4, 67% - at HN and 60% - at DF. Analysis of influence of various factors (statistically significant) on the response to therapy is presented in the Table.Table.Influence of various factors on the response to therapy with denosumab after 12 months of treatment (n=66)DXA sitePositive response on therapy is associated withNegative response on therapy is associated withL1-L4–- GC intake (> 3 months in anamnesis) (р = 0,034);- the beginning of GC intake after menopause (р = 0,023)Hip neck- higher concentration of the RF (initially and in dynamics) (р < 0,05);- the beginning of menopause later than RA onset (р = 0,024)- GC intake (> 3 months in anamnesis) (р = 0,024)Forearm (distal 1/3)- RF-positivity (р = 0,02)- back correlates with increase in erosion score and total SVH score: r = –0,360 (р < 0,05)Conclusion:After 12 months of therapy with denosumab in postmenopausal women with RA and OP it was shown the significant increase of BMD in L1-L4 and HN, a tendency to increase in DF. The mean change of BMD (%) after 12 months was +4,6% at L1-L4, at HN +2,8%, at DF +0,7%. Positive response on denosumab (BMD) was noted in 89% patients at L1-L4, 67% - at HN and 60% - at DF. Analysis of influence of factors on the response to therapy showed that positive response on therapy in NH and DF was associated with RF-positivity. The distinct contribution to the negative response in L1-L4 and HN was associated with GC intake (previous intake more than 3 months in the anamnesis) and purpose of the GC after menopause onset. Also, negative response in DF back correlated with increase in erosion score and total SVH score.Disclosure of Interests:None declared

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1432.2-1432
Author(s):  
N. Toroptsova ◽  
O. Dobrovolskaya ◽  
N. Demin ◽  
L. Shornikova

Background:Rheumatoid arthritis (RA) is a complex inflammatory disease that modifies body composition. Using the dual-energy x-ray absorptiometry (DXA) in RA patients could be a method for body composition changes detection.Objectives:To study the body composition using DXA in patients with RA.Methods:The study involved 79 women with RA, median age 60 [55; 65] years. The bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry using «Discovery A» (Hologic, USA). Assessment of body composition was carried out, using the program «Whole body». Sarcopenia (SP) was diagnosed as a decrease in appendicular mass index (AMI) <6.0 kg/m2. Osteoporosis (OP) was diagnosed as a decrease in T-score <-2.5 SD. Osteosarcopenia was determined when T-score was <-1.0 SD, AMI was <6.0 kg/m2, osteosarcopenic obesity - T-score was <-1.0 SD, AMI was <6.0 kg/m2and total fat was >35%.Results:The mean duration of RA was 9 [3; 11] years. The mean body mass index (BMI) was 27.6±4.8 kg/m2. Disease activity score in 28 joints-erythrocyte sedimentation rate was 4.5±1.3 points for the group. 39 (49.3%) patients used oral glucocorticoids continuously. Appendicular muscle mass and AMI were on average 17.8±3.0 kg and 6.8±1.0 kg/m2, respectively. AMI <6 kg/m2was detected in 20 (25.3%) patients. 56 (70.9%) women with RA had total fat > 35%, while only 22 (27.8%) of women with RA had obesity according to BMI (BMI >30 kg/m2). Isolated OP was found in 13 (16.5%), osteosarcopenia in 7 (8.9%) and osteosarcopenic obesity in 13 (16.5%) patients RA. No cases with isolated sarcopenia or sarcopenic obesity were detected. Only 3 (3.8%) patients did not have appendicular muscle mass, AMI and BMD decrease and overfat or obesity.Conclusion:About 97% women with RA had abnormal body composition phenotype: 16,5% - OP, 8.9% -osteosarcopenia, 16,5% - osteosarcopenic obesity and 54,4% - overfat.Disclosure of Interests:None declared


1992 ◽  
Vol 2 (2) ◽  
pp. 43-46
Author(s):  
U. Fusco ◽  
R. Capelli ◽  
A. Avai ◽  
M. Gerundini ◽  
L. Colombini ◽  
...  

Between 1980 and 1987 we have implanted 46 isoelastic cementless THR in 40 patients affected with rheumatoid arthritis. We have reviewed 38 hips clinically and by X-ray. The mean follow-up was 8,5 years. Harris hip scores ranged from 30.6 preoperatively to 73,4 post-operatively when reviewed. While on the other hand Merle D'Aubigné hip scores ranged from 7,06 pre-operatively to 15,59 post-operatively. All patients have been satisfied, and X-rays showed an improvement for both Charnely and Gruen X-ray score.


2019 ◽  
Vol 22 (1) ◽  
pp. 41-46
Author(s):  
Madhuchhanda Hazra Mou ◽  
Sadia Sultana ◽  
Pupree Mutsuddy ◽  
Suraya Sarmin ◽  
Naheed Khan ◽  
...  

Objective: Worldwide, osteoporosis in postmenopausal women is a common public health problem. The measurement of bone mineral density (BMD) of spine and hip using central dual energy X-ray absorptiometry (DXA) is the most standard technique to diagnose osteoporosis. But in many circumstances, measurement of spine or hip BMD is quite difficult to carry out where wrist BMD can be used as an alternative. Moreover, wrist BMD can be done with smaller, cheaper, portable peripheral devices for screening osteoporosis at primary health care level. The objective of the study was to explore the agreement of wrist BMD with spine and hip BMD in postmenopausal women. Patients and Methods: This observational, cross sectional study was carried out at National Institute of Nuclear Medicine & Allied Sciences (NINMAS), Bangabandhu Sheikh Mujib Medical University (BSMMU) campus, from July 2017 to June 2018. A total of 110 postmenopausal women referred to NINMAS for BMD measurement were enrolled in this study after fulfilling selection criteria.  BMD of spine, right and left hip and wrist of enrolled subjects were measured by dual energy X-ray absorptiometry (DXA) scan by Stratos DR Bone densitometer. Results:  Agreement analysis done by kappa statistics revealed kappa value of 0.930 (p<0.05), 0.782 (p<0.05) and 0.635 (p<0.05) between wrist and spine BMD, wrist and right hip BMD and wrist and left hip BMD, respectively. In Bland-Altman analysis, the mean difference of T-score measured by wrist and spine was -0.007 ± 1.361, wrist and right hip was -0.645 ± 1.271 and wrist and left hip was -0.450 ± 1.259 with 95% of differences were found in between -2.674 and 2.660, -3.136 and 1.846 and -2.917 and 2.017, respectively. Positive significant Pearson’s correlation was observed between wrist BMD and spine BMD (r=0.664; p=0.001), wrist BMD and right hip BMD (r=0.719; p=0.001) and wrist BMD and left hip BMD (r=0.727; p=0.001). Conclusion: This study results showed an excellent kappa agreement between wrist and spine BMD with good kappa agreement of wrist with right and left hip BMD as well as in Bland-Altman analysis, the mean differences of T-score between wrist andspine, wrist and right hip and wrist and left hip were small. The biases between the methods were considered not significant suggesting that these sites can be used interchangeably for measurement of BMD. Hence, wrist BMD can be used with regular skeletal sites (spine and hip) as an effective method of diagnosing osteopenia and osteoporosis by DXA where spine or hip BMD is difficult to carry out as well as it can be used for osteoporosis screening at primary health care level by portable peripheral DXA device to initiate early treatment to reduce fracture risks. Bangladesh J. Nuclear Med. 22(1): 41-46, Jan 2019  


1996 ◽  
Vol 14 (1) ◽  
pp. 78-84 ◽  
Author(s):  
T J Powles ◽  
T Hickish ◽  
J A Kanis ◽  
A Tidy ◽  
S Ashley

PURPOSE Tamoxifen is an effective treatment for metastatic and primary breast cancer and is now being evaluated as a chemoprevention agent in healthy women. Any long-term effects on estrogen-sensitive tissues such as bone may have important therapeutic implications. METHODS We measured bone mineral density (BMD) in the lumbar spine and hip using dual-energy x-ray absorptiometry (DXA) in premenopausal and postmenopausal healthy women who participated in our placebo-controlled tamoxifen chemoprevention of breast cancer trial. RESULTS BMD data are now available from 179 women for this analysis. In premenopausal women, BMD decreased progressively in the lumbar spine (P < .001) and in the hip (P < .05) for women on tamoxifen, but not those on placebo. The mean annual loss in lumbar BMD per year over the 3-year study period in tamoxifen-treated compliant women who remained premenopausal throughout the study period was 1.44% (1.88% calculated on an intent-to-treat basis) compared with a small gain of 0.24% per annum for women on placebo (P < .001). Tamoxifen had the opposite effect in postmenopausal women. The mean annual increase in BMD for women on tamoxifen was 1.17% in the spine (P < .005) and 1.71% in the hip (P < .001) compared with a noninsignificant loss for women on placebo. CONCLUSION These results indicate that tamoxifen treatment is associated with a significant loss of BMD in premenopausal women, whereas it prevents bone loss in postmenopausal women. These adverse and beneficial effects of tamoxifen should be considered in the assessment of the therapeutic benefits for both the adjuvant treatment and the chemoprevention of breast cancer.


Author(s):  
William F. Tivol ◽  
Murray Vernon King ◽  
D. F. Parsons

Feasibility of isomorphous substitution in electron diffraction is supported by a calculation of the mean alteration of the electron-diffraction structure factors for hemoglobin crystals caused by substituting two mercury atoms per molecule, following Green, Ingram & Perutz, but with allowance for the proportionality of f to Z3/4 for electron diffraction. This yields a mean net change in F of 12.5%, as contrasted with 22.8% for x-ray diffraction.Use of the hydration chamber in electron diffraction opens prospects for examining many proteins that yield only very thin crystals not suitable for x-ray diffraction. Examination in the wet state avoids treatments that could cause translocation of the heavy-atom labels or distortion of the crystal. Combined with low-fluence techniques, it enables study of the protein in a state as close to native as possible.We have undertaken a study of crystals of rat hemoglobin by electron diffraction in the wet state. Rat hemoglobin offers a certain advantage for hydration-chamber work over other hemoglobins in that it can be crystallized from distilled water instead of salt solutions.


Author(s):  
Noriyuki Kuwano ◽  
Masaru Itakura ◽  
Kensuke Oki

Pd-Ce alloys exhibit various anomalies in physical properties due to mixed valences of Ce, and the anomalies are thought to be strongly related with the crystal structures. Since Pd and Ce are both heavy elements, relative magnitudes of (fcc-fpd) are so small compared with <f> that superlattice reflections, even if any, sometimes cannot be detected in conventional x-ray powder patterns, where fee and fpd are atomic scattering factors of Ce and Pd, and <f> the mean value in the crystal. However, superlattices in Pd-Ce alloys can be analyzed by electron microscopy, thanks to the high detectability of electron diffraction. In this work, we investigated modulated superstructures in alloys with 12.5 and 15.0 at.%Ce.Ingots of Pd-Ce alloys were prepared in an arc furnace under atmosphere of ultra high purity argon. The disc specimens cut out from the ingots were heat-treated in vacuum and electrothinned to electron transparency by a jet method.


1960 ◽  
Vol XXXIV (I) ◽  
pp. 45-50 ◽  
Author(s):  
J. L. Kalliomäki ◽  
Lauri Rauramo

ABSTRACT The authors have endeavoured to clarify the frequency of the hyperoestrogenismus syndrome in women with rheumatoid arthritis, aged 17–38 years, by means of clinical and cytologic studies, and by hormonal analyses. The material comprises 32 patients. Of these, 30 were suitable for cytologic observation. In 5 (17 %) of these 30 patients, the hyperoestrogenismus syndrome (17 %) may be considered definitely established. Aggravation of the joint symptoms in the pre-menstrual phase was reported by 41 % of the patients. Values for excretion of oestrogen exceeding 200 mouse units/24 hours were noted one week before menstrual bleeding in 8 of 19 women; the mean for oestrogen excretion was 268 mouse units/24 hours. Gonadotrophins were studied in the same urine samples, and the mean excretion was 22 mouse units/24 hours (range 7–65 m. u.). The excretion mean for 17-ketosteroids, simultaneously studied, was 9.1 mg/24 hours (range 2.3–18.0 mg). Side-finding in the material were made: incipient cervical cancer in one patient, ovarial tumour in one, and trichomoniasis in seven.


Reproduction ◽  
2000 ◽  
pp. 331-336 ◽  
Author(s):  
L Holm ◽  
H Ekwall ◽  
GJ Wishart ◽  
Y Ridderstrale

Sperm storage tubules from the utero-vaginal junction of chickens, quails and turkeys were analysed for calcium and zinc using X-ray microanalysis of ultra-rapidly frozen tissue in a scanning electron microscope. This technique enabled the tubular fluid surrounding the stored spermatozoa and the intracellular content of the cells of the sperm storage tubules to be analysed separately and, by using standards with known concentrations, their elemental concentrations were estimated. The mean (+/- SEM) concentration of calcium in the tubular fluid from chickens, quails and turkeys was 17 +/- 3, 19 +/- 3 and 17 +/- 4 mmol kg(-1) wet weight, respectively. The intracellular calcium concentration of the cells of the tubules did not differ significantly from these values and was also similar in the mucosal epithelial cells of the utero-vaginal junction. Zinc was localized in the cells of turkey sperm storage tubules and tubular fluid, but at low concentrations. No zinc could be detected in corresponding structures from chickens and quails. The concentration of calcium in the tubular fluid is within the range known to inhibit the motility of spermatozoa, supporting this function for calcium during storage. Zinc is known to depress turkey sperm metabolism and it may also be involved in inducing quiescence of spermatozoa during storage in this species.


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