[Efficacy and safety of bivalos therapy for postmenopausal osteoporosis. Results of Russian multicenter trial].

AIM: To study effects of one-year therapy with bivalos on mineral bone density (MBD) of the spine in patients with postmenopausal osteoporosis (PMO), effects of bivalos (strontium ranelate) on MBD of the neck of the femur and femur, the levels of bone metabolism markers, quality of life, tolerance of long-term therapy. MATERIAL AND METHODS: The study was made of 60 females aged 54-75 years with PMO. MBD was measured with x-ray absorptiometry in the vertebra and proximal femur. Bone markers in blood serum were detected by enzyme immunoassay. RESULTS: After a year of taking bivalos MBD in lumbar vertebra increased by 4.68 +/- 4.94%, in the neck of the femur--by 2.0 +/- 4.29%, in the proximal femur--by 3.10 +/- 3.34%. A significant 19.5% rise in bone alkaline phosphatase and a 16.5% fall in the level of CT were noted showing a stimulating effect of bivalos on bone formation and an inhibiting effect--on bone tissue resorption. Bivalos treatment raised quality of life of the patients: better motility, regress of depression, improved self-appraisal, decreased number of patients with pain in the spine, attenuated pain. The drug was well tolerated, unwanted effects arose in 15% patients, discontinuation of the drug because of toxicity occurred in 5%. Serious side effects were not observed. CONCLUSION: Strontium ranelate is effective in PMO and is well tolerated.

[Genetics of osteoporosis].

Osteoporosis is a common disease with a strong genetic componenet characterized by reduced bone mass and increased risk of fragility fractures. Twins and family studies have shown that the heritability of bone mineral density (BMD) and other determinants of fracture risk - such as ultrasound properties of bone, skeletal geometry, and bone turnover - are high, although heritability of fracture is modest. In this article, some important gene identifications of the last years such as vitamin receptor, estrogen receptor alpha, alpha 1 chain of type I collagen, low density lipoprotein receptor - related protein 5, bone morphogenic proteins 2 and 4, transforming growth factor beta 1, receptor activator of NF-kappa-B, receptor activator of NF-kappa-B ligand, osteoprotegerin and their contribution to the understanding of the genetic regulation of bone mass and susceptibility to osteoporosis are present.

[Combined medication ARTRA in the treatment of osteoarthrosis].

AIM: To study clinical effectiveness, safety and duration of the effect of combined medication ARTRA (500 mg glucosamine hydrochloride+500 mg chondroitine sulphate) in osteoarthrosis. MATERIAL AND METHODS: Ninety women aged 40-75 suffering from knee OA and satisfying diagnostic criteria for OA of American Rheumatological Committee having x-ray II-III stages according to Kellgren-Lawrence; with distinct pain syndrome (pain intensity at walking 40 mm and more by the analogue visual scale); taking NSAIDS regularly during 30 days within 3 months before the study were enrolled in the study. The patients were randomly divided into 2 groups: 45 patients of the study group taking 1 tablet ARTRA 2 times a day within the first month, than 1 tablet a day within the following 5 months and diclofenac sodium 50 mg 2 times a day with gradual decrease of the dosage as the pain was decreasing; 45 patients of the control group taking only diclofenac sodium 50 mg twice a day during 6 months. Clinical examination of the patients was done before the treatment, 30, 120 and 180 days after the study. Long-term effects of ARTRA was evaluated 3 months after the study. The treatment efficacy was assessed by WOMAC index, daily need in NSAIDS intake, evaluation of the efficacy by the patient and the doctor. RESULTS: The true WOMAC index decreased in 4 and 6 months of therapy in the study group (p < 0.03). 3 months after the treatment the study group patients experienced continuous reduction of the functional index and pain intensity unlike of the control patients experiencing a pain increase and worsening of joints functional ability. When analysing pain syndrome according to VAS, after 4 months of the treatment pain was relieved more in the study group (p = 0.008). The differences were stable for 6 months. On aftertreatment month 3 pain syndrome tended to attenuation in the study group but to intensification in the controls. While taking ARTRA, the patients decreased their need in NSAIDS intake (diclofenac). After 1 month of therapy 4.5% patients gave up taking diclofenac; after 4--20%, after 6--40%. Objective and subjective effects did not differ much (94 and 90%, respectively). ARTRA tolerability was very good. None of the patients of the study group discontinued therapy because of side effects, in the control group 14 patients gave up diclofenac because of the adverse effects. CONCLUSION: Combined ARTRA medication decreases pain, improves joint function. Regular intake of ARTRA helps decrease NSAIDS dosage or discontinue intake in many cases. ARTRA is very well tolerated and is safe. ARTRA has an evident long lasting effect.

[Allele polymorphism of alkaline phosphatase, acid soluble phosphatase, and vitamin D-binding protein genes in postmenopausal osteoporosis]. / Allel'nyi polimorfizm genov shchelochnoi fosfatazy, kisloi rastvorimoi fosfatazy i belka, sviazyvaiushchego vitamin D, pri postklimaktericheskom osteoporoze.

AIM: To study polymorphism of genes involved in mechanisms regulating metabolism of bone tissue: alkaline (ALPL) and acid (ACP1) phosphatases, vitamin D-binding protein (GC); to ascertain associations of their genotypes and alleles with osteoporosis (OP) and mineral density of spinal and femoral bone tissue (BTMD). MATERIAL AND METHODS: Relevant genetic examination was made in 70 females with OP diagnosed by the WHO criteria (1994) aged 60-79 years (mean age 71.0 +/- 6.2 years) and 51 OP-free females in the same age interval (mean age 69.0 +/- 5.6 years). Polymorphic sites of the genes were examined by polymerase chain reaction. Trinucleotide repeat, ARG105GLN polymorphism of restrictive fragment length (PRFL), [GC, TRH420LYS] PRFL were studied for ALPL gene, ACP1 gene and GC gene, respectively. RESULTS: Association was found between frequencies of genotypes SS, 2F and FS, F allele of GC gene with OP as well as between PRFL of the spine, femur and some GC genotypes in OP women. Genes ALPL and ACP1 were not associated with OP. CONCLUSION: It is suggested that genotypes SS, 2F and FS have marked functional differences in fixation and transport of vitamin D active metabolites involved in metabolism of bone tissue in OP.

[Vitrum osteomag in prevention of osteoporosis in postmenopausal women: results of the comparative open multicenter trial]. / Vitrum osteomag v profilaktike osteoporoza u zhenshchin v postmenopauze: rezul'taty sravnitel'nogo otkrytogo mnogotsentrovogo issledovaniia.

AIM: To investigate efficacy, tolerance and safety of the drug vitrum osteomag one tablet of which contains 600 mg calcium (1500 mg calcium carbonate), 200 IU of cholecalcepherol, 40 mg of magnesium, zinc (7.5 mg), copper (1 mg), manganese (1.8 mg) and boron (250 mcg) in women with osteopenia for prevention of osteoporosis. MATERIAL AND METHODS: A multicenter comparative open trial of vitrum osteomag influence on mineral bone density (MBD), change of pain syndrome in bones, index of calcium-phosphorous metabolism covered 334 postmenopausal women with osteopenia. MBD was measured in low-back spine and proximal part of the hip with DEXA method. All the patients were divided into 3 groups: 125 women taking 2 tablets of vitrum osteomag daily for 12 months (group 1); 111 women taking 1500 mg calcium carbonate (group 2); 96 women--control group (only observation). RESULTS: Vitrum osteomag relieved pain in the back and joints, had a positive effect on bone density (+1.5%) and proximal parts of the hip (0.6-0.93%) exceeding the effect of calcium carbonate only which preserves the initial MBD in low back spine but does not prevent bone loss in the hip. MBD dynamics in patients given vitrum osteomag differs essentially from one in the control group (from -1.9 to -2.91%) which demonstrates a reliable preventive anti-osteoporotic effect of this medication. The drug increases the level of general and ionized calcium in blood but does not cause hypercalcemia lowering the level of parathormone in blood. The rate of side effects in group 1 was 14.4% and did not differ much from that in group 2 (16.2%). CONCLUSION: The results of the study allow to recommend vitrum osteomag for prophylaxis of a rapid loss of bone tissue mineral density.

[Issues of osteoporosis in present-day medicine]. / Problema osteoporoza v sovremennoi meditsine.

Osteoporosis (OP) is a systemic metabolic lesion of the skeleton involving a reduced osseous tissue weight and an impaired microarchitectonics, which worsens the bone strength and contributes to a higher risk of bone fractures. An essential spread of OP and of osteoporotic fractures among populations in various countries, including Russia, a high-severity outcome, and big economic expenses related with treatment and rehabilitation are indicative of a high social OP significance. OP is a multi-factor pathology provoked by impaired processes in osseous remodeling with a higher resorption of osseous tissue and a reduced osteogenesis. A study of molecular mechanisms of intercellular interaction in OP resulted in discovering new elements in the family of tumor necrosis factor (TNF) and their ligands and receptors (RANKL-RANK-OPG), which are of primary importance in osteoclastogenesis and which are molecular mediators in many regulatory effects. The key drugs applicable to prevention and treatment of OP are also described in the article. The current methods of OP prevention and treatment improve the bone quality and reduce the incidence rate of fracture in an essential share of patients.

[Bone mineral density in idiopathic inflammatory myopathies]. / Mineral'naia plotnost' kostnoi tkani pri idiopaticheskikh vospalitel'nykh miopatiiakh.

The study was undertaken to examine the impact of glucocorticoid therapy (GCT) on mineral bone density (MBD) in patients with idiopathic inflammatory myopathies. Double-energy X-ray absorptiometry was used to determine MBD of the vertebral column and proximal femur in 42 females (30 with the preserved menstrual cycle (PMC), 12 in postmenopause (PMP) with polymyositis/dermatomyositis (PM/DM). All the patients received GCT. A random population sample including 106 females aged 20 to 69 years formed a control group. MBD of the neck of the femur was significantly lower in patients from all age groups, in the lumbar vertebral column in young (20-29 years) and old (over 50 years) females than in the controls. The development of osteoporosis (OP) was more frequently observed in PMP females: OP in the lumbar spine was in 16.7 and 66.7% of the PMC and PMP females, respectively; that in the neck of the femur was in 11 and 33%. There was no relationship between MBD and the specific features of GCT, namely the duration, cumulative dose, and the maximum dose. There was a reduction in MBD in patients with PM/DM on GCT in all age groups, more frequently in PMP patients.

[Bone mineral density and risk factors for developing osteoporosis in bronchial asthma patients]. / Mineral'naia plotnost' kostnoi tkani i faktory riska razvitiia osteoporoza u bol'nykh bronkhialnoi astmoi.

AIM: To estimate mineral bone tissue density (MBTD) and risk factors for osteoporosis in patients with bronchial asthma (BA). MATERIAL AND METHODS: A cross-sectional study included 119 patients (48 males and 71 females) aged 18 to 49 years who had no diseases or states that can induce MBTD, except BA. The patients were divided into 3 groups: 1) those untreated with glucocorticoids (GC); 2) those who received inhaled GC; and 3) those who permanently took oral and inhaled GC. The patients underwent questionnaire survey, double-power X-ray absorption of the lumbar vertebral column and proximal femur, and X-ray study; forced expiratory volume per sec and peak expiratory function were measured. RESULTS: In Group 1 patients, there was a high incidence of osteopenia that increased with the severity of BA. About 2.5-year therapy with inhaled GC in large and small doses had no impact on MBTD. The prolonged use of systemic GC caused a marked reduction in MBTD and led to the development of osteoporetic fractures. Changes were detected in both the lumbar spine and proximal femur. In males and females, MBTD decreases were equal. MBTD correlated with the duration of GC therapy and with age at its initiation, but not with the daily dose of GC. In 15.4% of the patients, MBTD remained in the normal range despite the prolonged use of GC in large doses. Osteoporetic fractures were observed at the values of MBTD, which had not reached the stage of osteoporosis according to the WHO criteria, which was indicative of qualitative GC-induced bone tissue changes. CONCLUSION: GC is an important, but not alone, risk factor for osteoporosis in asthmatic patients. The high rate of low MBTD among the patients receiving no GC suggests that it is necessary to make an early diagnosis and to perform rational treatments.

[Relations between ankylosing spondyloarthritis and HLA-B27 in various ethnic groups in Russia]. / Vzaimosviaz' ankiloziruiushchego spondiloartrita i HLA-B27 v nekotorykh étnicheskikh gruppakh Rossii.

AIM: To characterize relationship between prevalence of ankylosing spondylarthritis (ASA) and incidence rate of HLA-B27 in genotypically different ethnic groups of Russia with interpolation of the results to other populations. MATERIAL AND METHODS: 2287 individuals from genotypically different ethnic groups were examined in overall one-stage epidemiological trial. RESULTS: Prevalence of ASA in ethnic groups ranged from 0.2 to 2.0% while occurrence of HLA0B27--from 15 to 40%. Rate of correlation between the disease prevalence and incidence of B27 was 0.82. The equation for calculation of ASA incidence rate by HLA-B27 incidence was devised: AC(%) = -0.40 + 0.06x. CONCLUSION: In most world populations prevalence of ASA correlates with population frequency HLA-B27 though in some ethnic groups this correlation is absent. Consequently, ASA is genetically heterogenous.

[Spondylarthropathies and rheumatoid arthritis in some Finno-Ugrian populations in Russia]. / Spondiloartropatii i revmatoidnyi artrit v nekotorykh ugro-finskikh populiatsiiakh Rossii.

AIM: Determination of the prevalence of spondylarthropathies (SAP) and rheumatoid arthritis (RA) among Finno-Ugrian population of Russia. MATERIALS AND METHODS: A one stage expedition trial was made of representative samples of Mordovian and Mari populations including 1312 citizens aged over 14 years. RESULTS: Incidence rate of SAP among Mordovian and Mari examinees was 0.7 and 0.2%, respectively, ankylosing spondylitis being most frequent finding. RA occurred in 2.5 and 0.6%, respectively. All the RA cases were females without family history of this disease. CONCLUSION: SAP and RA prevalence among Mordovian and Mari populations was high but their course is more favorable than among other population of Russia.

[Population-based study of antibodies to certain potential infectious triggers of spondylarthropathies: a study of Ugro-Finnish population of Russia]. / Populiatsionnoe issledovanie antitel k nekotorym potentsial'nym infektsionnym triggeram spondiloartropatii: izuchenie nekotorykh ugro-finskikh populiatsii Rossii.

A study was made of antibodies to some enterobacteria--potential triggers of spondyloarthropathies in population of mordva characterized by higher frequency of HLA-B27. 141 and 148 plasm samples were taken from erzya and moksha subpopulations, respectively. Enzyme immunoassay has detected specific antibodies IgA, IgM, IgG to Salmonella, Yersinia, Campylobacter and Klebsiella. Specific immune response in the mordva population appeared to depend on gender, age and nationality but not HLA-B27. In the study population the role of Klebsiella infection in development of ankylosing spondylarthritis was not confirmed though the number of the patients was not sufficient to reject this suggestion.

[Population study of antibodies to some potential pathogens of spondyloarthopathies: the study of the Chukotka population]. / Populiatsionnoe issledovanie antitel k nekotorym potentsial'nym agentam spondiloartropatii: izuchenie populiatsii Chukotki.

The paper presents the results of the study of specific immune response stimulated by some enterobacteria in populations with high incidence of HLA-B27. A, M and G antibodies to Yersinia, Clebsiella, Salmonella and Campilobacter were studied on 292 plasma samples. The levels of the antibodies varied with anthropological parameters of the examinees (gender, age, nationality). The presence of the gene HLA-B27 in the genotype levels gender dimorphism of the specific humoral immune response. This may be of importance in pathogenesis of spondyloarthropathies which occur more frequently in men.

[The prevalence of rheumatoid arthritis and the rheumatoid factor in the native inhabitants of northeastern Siberia]. / Rasprostranennost' revmatoidnogo artrita i revmatoidnogo faktora u korennykh zhitelei Severo-Vostochnoi Sibiri.

AIM: The study of rheumatoid arthritis (RA) and rheumatoid factor (RF) prevalence among residents of eastern Chukotka--Eskimos and Chukchi. MATERIALS AND METHODS: Simultaneous total survey covered 974 of 1176(83.3%) residents of 4 villages in the eastern Chukotka. RESULTS: RA was diagnosed in 7(0.7%) examines. Clinical picture of the disease was characterized by for the most part symmetric affection of hand and feet joints, absence of systemic manifestations, favourable course and frequent absence of RF. RF positive titers (1:160 and higher) occurred in 23 of 804 examinees (2.9%), among Eskimos--6%. This was significantly higher than in Chukchi (2.0%) and in subjects of mixed nationality (1.3%). CONCLUSION: Prevalence and clinical picture of RA in residents of northeast Siberia were comparable with such observed in other epidemiological surveys in Russia and Alaska.

[Structum (chondroitin sulfate)--a new agent for the treatment of osteoarthrosis]. / Struktum (khondroitinsul'fat(--novoe sredstvo dlia lecheniia osteoartroza.

AIM: To study efficiency and tolerance of Structum in gonarthrosis patients as well as duration of its effect after discontinuation. MATERIALS AND METHODS: 100 patients with femorotibial gonarthrosis aged 45 years and older entered an open randomised trial. They had knee joint arthrosis satisfying diagnostic criteria OA ACR at stage II-III according to Kellgren-Lawrence with pain syndrome. Walking pain intensity was > or = 30 mm by the visual analogue scale (VAS), Leken total functional index > or = 4 and < or = 11. Antiinflammatory drugs (AI) were regularly taken for 30 days for the 3 pretreatment months. 50 patients of the study group received Structum and ibuprofen (1200 mg/day) for 6 months. 50 patients of the control group received ibuprofen only. The two groups were followed up for 3 months. Clinical examination was made monthly. RESULTS: There were significant differences between the groups by the Leken's index (p < 0.005), VAS, pain, daily AI drug requirement. Structum proved more effective. Tolerance was good. Side effects were observed only in two patients (diarrhea and nausea). In the control group, side effects made 15 patients to discontinue the treatment. CONCLUSION: Structum is a new effective drug against gonarthrosis which reduces pain, improves joint function. It is well tolerated and allows to diminish the dose of AI drugs. The response to Structum persisted for 3 months after the treatment.

[Comparative study of epidemiology of spondylarthropathies in indigenous population of the Chukot peninsula and Alaska]. / Sravnitel'noe izuchenie épidemiologii spondiloartropatii sredi korennykh zhitelei Chukotki i Aliaski.

UNLABELLED: The paper sums up the many-year cooperative Russian-American studies of the epidemiology of spondylarthropathies in the arctic populations of the Chukot Peninsula and Alaska. AIM: Comparison of the epidemiology of spondylarthropathies in the indigenous population of the Chukot Peninsula and Alaska. MATERIALS AND METHODS: A universal design of investigation with the same diagnostic criteria was used in both countries. A total of 974 indigenous residents of the Chukot Peninsula were examined simultaneously, on the Alaska the sampling was formed as the residents applied for care. RESULTS: In both regions the study revealed 1) a high incidence of HLA-B27, reaching 40% in the Chukot Eskimos; 2) a similarly high incidence of spondylarthropathies varying from 2 to 3.4%; 3) a similar spectrum of diseases, including, primarily, ankylosing spondylarthritis and Reiter's syndrome and undifferentiated spondylarthropathies and (rarely) psoriatic arthritis. Among HLA-B27 positive adults, the incidence of spondylarthropathies in all groups is 4.2% and of ankylosing spondylarthritis 1.5%. CONCLUSION: A high incidence of spondylarthropathies, varying from 2 to 3.4%, was revealed in the Arctic populations of the Chukot Peninsula and Alaska with a high incidence of HLA-B27 antigen. Although the spectrum of detected diseases was similar in the two groups, ankylosing sponditis was more incident on the Chukot Peninsula, whereas on the Alaska reactive arthritis and nondifferentiated spondylarthropathies predominated, which can be explained by difference in the methods of examination.

[Epidemiology of rheumatic diseases in historical aspect]. / Epidemiologiia revmaticheskikh zabolevanii v istoricheskom aspekte.

The paper summarizes the results of the long-term study of the epidemiology of rheumatic diseases, which has been carried out by the Institute of Rheumatology. The main directions of the study are the development and improvement of diagnostic criteria, the prevalence and incidence of rheumatic diseases among urban and rural populations, at industrial enterprises, in different ethnic groups, genetic and environmental risk factors, disability, the development and introduction of preventive and rehabilitative programmes of drug therapy, etc. A number of combined national programmes was carried out. The paper presents specific results of their implementation.

[Spondyloarthropathies and HLA-B27 subtypes in the populations of the Russian North]. / Spondiloartropatii i subtipy HLA-B27 v nekotorykh populiatsiiakh Severa Rossii.

The aim of the study was to investigate the role of HLA-B27 subtypes in development of ankylosing spondylitis and other seronegative spondylarthropathies. Using oligotyping techniques we studied native DNA of 219 HLA-B27 positive natives: 88 Chukotka residents and 131 Mordovians (Russian Ugro-Finnish population). Only subtypes HLA-B*2705 and B*2702 were revealed. A dominant subtype of HLA-B27 among the natives was HLA-B*2705: 99% among residents of Chukotka and 86% among Mordovians. It was established that among spondylarthropathic patients the frequency of B*2705 does not differ from its incidence in the studied populations. The data support the suggestion that several B27 subtypes and common genetic determinant of B27 gene may be involved in pathogenesis of spondylarthropathy.

[An epidemiological study of sacroiliitis among the native inhabitants of Chukotka]. / Epidemiologicheskoe issledovanie sakroileita sredi korennykh zhitelei Chukotki.

For determination of sacroiliitis frequency among natives of Chukotka peninsula a cross-over epidemiological study was conducted. A total of 975 subjects aged 6 years and older were examined. 324 of them (33.2%) had low back pain. X-ray of the pelvis was made in 239 of 324 patients. It was found that sacroiliitis incidence in Chukotka natives makes up 11.3%. There were marked differences in sex distribution: in males 17.1%, in females 5.7%, RR = 3.9. Out of Chukotka natives with low back pain 2.5% had ankylosing spondylitis, of patients with sacroiliitis 30%. A prospective study of patients with sacroiliitis recorded development of ankylosing spondylitis in 17% of the cases 4 years after the disease onset.

[The use of rumalon in gonarthrosis]. / Primenenie rumalona pri gonartroze.

An open prospective study in 100 industrial workers suffering from gonarthrosis has been performed 80 patients were treated with rumalon, 30 ml injections, twice/year, for 3 years in combination with ibuprofen film tabs, max daily dose (when required) 1800 mg. 20 patients have received ibuprofen only, the same dose. The control group was matched by sex, age, profession and duration of service. Significant differences for functional index of Lequesne between the two groups were detected after 1.5 years of the treatment (p < 0.05). An increase in the range of movements in knee joints in rumalon group was detected in comparison with the control group (p < 0.04). The improvement of joint function was achieved in 87% of the rumalon group patients while in the control group half of the patients got aggravation. The analysis of x-ray data has revealed no significant differences between the two groups. Rumalon is an effective agent against pain syndrome in gonarthrosis patients, preserves and improves joint function. Rumalon should be administered for long-term periods.