[Experience in using Prolia in patients with postmenopausal osteoporosis in clinical practice]. / Opyt primeneniia preparata Prolia u patsientok s postmenopauzal'nym osteoporozom v klinicheskoi praktike.

AIM: To evaluate the efficiency and safety of long-term Prolia therapy in patients with postmenopausal osteoporosis (OP). SUBJECTS AND METHODS: The open prospective study enrolled 98 women (mean age, 68±9 years; mean menopause duration, 17±4 years) with postmenopausal OP, who were followed up in an outpatient setting at the National Medical Research Center for Preventive Medicine and who had been treated with denosumab 60 mg subcutaneously every 6 months for 12 months or more. The maximum follow-up period was 4 years: 48, 29, 11, and 10 patients were treated for 12, 24, 36, and 48 months, respectively. The patients were allocated into 2 groups: those who received and those who had not previously received antiosteoporotic therapy. Bone mineral density (BMD) was measured using dual-energy X-ray densitometry of the lumbar spine (LI-LIV) and proximal femur (PF). The ten-year probability of major osteoporotic fractures was estimated once in 72 patients not previously receiving antiosteoporotic therapy before the prescription of denosumab. RESULTS: In the patients not previously receiving therapy, the median 10-year probability of major fractures using the FRAX algorithm was 14.9%; that of femoral neck (FN) fractures was 3.7%. During denosumab treatment, the BMD increase in the lumbar spine was 4.2% at 12 months, 7.5% at 24 months, was 8.8% at 36 months; that in FN was 3.1, 3.9, and 5.3%, that in PF was 2.8, 4.1, and 5%; and that in the 1/3 forearm was 0.9, 1.4, and 2.6%, respectively (p < 0.001). In the persons receiving and not previously receiving the therapy, the BMD increase was similar, i.e. there was an additional positive effect when switching to denosumab. The decrease in the serum concentration of C-terminal telopeptide of type I collagen (CTX-I) was 54% at 6 months after initiation of denosumab therapy (p < 0.001) and 72% at 12 months (p<0.001); and the achieved marker level remained unchanged at 48 months. Transition from the OP zone to osteopenia one was noted in 23 patients with low BMD (T-score -2.5 SD) in LI-LII and in 12 patients with that in FN at 12 months of denosumab therapy and this was in 25 patients at 24 months. Nine-eight patients receiving the first Prolia injection refused to continue treatment on their own; adverse events were not the reason for drug discontinuation. CONCLUSION: Therapy with denosumab was effective in increasing BMD in routine outpatient practice and in allowing 25% of patients to achieve target values of this indicator. The marked decrease in the level of the bone resorption marker STX suggested that the drug had antiresorptive potency. The frequency of adverse reactions was low, confirming the good tolerability and safety profile of the drug. The convenience of the scheme and route of drug administration contributed to strict compliance with the doctor's recommendations. Denosumab was effective in increasing BMD not only in untreated patients, but also in those who had previously received antiosteoporotic therapy. The pharmacokinetic characteristics of denosumab, which contribute to its uniform distribution in trabecular and cortical bone tissue, regardless of active bone remodeling, and the fact that the clearance of the drug is independent of kidney function offer an advantage of administering the drug to patients with significant loss of FN and radius BMD and of reducing kidney function.

[Associations of lipoproteins with bone mass in postmenopausal women].

AIM: To study an association between blood lipid composition and bone mass in Russian postmenopausal women. SUBJECTS AND METHODS: The cross-sectional study included 373 postmenopausal women aged 45-80 years who were examined to diagnose osteoporosis in outpatient settings. Height, body weight, and waist and hip circumferences (WC and HC) were measured before densitometry. Quetelet's index was calculated as a ratio of weight (kg) to height (m2). The concentration of lipids and apolipoproteins (apo) AІ and B were measured by enzyme immunoassay. Bone mineral density (BMD) in the spine and proximal femur (PF) was estimated by dual-energy X-ray absorptiometry. RESULTS: According to bone mass, the patients were divided into three groups: 1) osteoporosis (OP); 2) osteopenia; 3) normal BMD. The levels of total cholesterol and high-density lipoprotein (HDL) cholesterol were significantly higher in the postmenopausal women with OP than in those with normal bone mass. There was a negative correlation of cholesterol and HDL cholesterol levels with lumbar spine BMD and that of HDL levels with BMD in the femoral neck (FN) and entire PF. The level of lipoprotein (a) (LPa) was significantly lower in the group of patients with OP and positively correlated with BMD in FN and entire PF. After adjustment for age, the duration of menopause, Quetelet's index, and WC/HC association remained only between LPa and FN BMD. CONCLUSION: Multivariate regression analysis failed to confirm a trend towards decreased BMD and increased HDL cholesterol. This suggests that the association of HDL cholesterol with bone mass is apparently mediated by other factors and, above all, with age, postmenopausal hormonal status and body weight.

[Preliminary results of an open-label observational study evaluating the efficacy and safety of Prolia used in women with postmenopausal osteoporosis].

AIM: To evaluate the efficacy and safety of Denosumab (Prolia), a first-line osteoporosis (OP) medication that is a fully human monoclonal antibody to the receptor activator of nuclear factor xB ligand (RANKL), within an open-label observational study. SUBJECTS AND METHODS: Patients aged 50 years or older with postmenopausal OP, who were treated with Prolia in clinical practice, were examined. The concentrations of the bone resorption (BR) marker of C-terminal telopeptide and other laboratory indicators (total serum calcium, total alkaline phosphatase, and creatinine) were measured following 3 months. Adverse drug reactions were recorded. RESULTS: Three months after initiation of the investigation, there was a significant decrease in the BR marker C-terminal telopeptide (by 89%; p<0.0001). There were rare adverse reactions: hypocalcemia in 3 (5.9%) patients, arthralgias in 2 (3.9%), and eczema in 1 (1.9%). There were neither serious adverse events nor study withdrawal cases. CONCLUSION: The preliminary results of the open-label study of Prolia in postmenopausal OP suggest that the significantly lower BR activity determines the efficacy of this drug and its high safety.

[Cardiovascular diseases and osteoporosis: what is common?].

The review analyzes the possible effect of cardiac drugs on the course of osteoporosis (OP). The fact that atherosclerosis and OP share the mechanisms of development, among which the enhanced activity of the sympathetic part of the autonomic nervous system and endothelial dysfunction are most important, is beyond question now. In this connection, beta-adrenoblockers, nebivolol in particular, attract attention. Nebivolol is known to be a selective beta1-adrenoblocker that has an additional vasodilator property, by stimulating the synthesis of nitric oxide. This may serve to increase bone mineral density and slow down the progression of OP. At the same time, most investigations in this area are retrospective therefore final conclusions call for randomized prospective studies that will be able to evaluate more objectively the effect of cardiac drugs on the prevention of OP or its progression delay.

[Characteristics of local human skeleton reactions to microgravity and drug treatment of osteoporosis in clinic].

Analysis of the results of long-term investigations of bones in cosmonauts flown on the orbital station MIR and International space station (n = 80) was performed. Theoretically predicted (evolutionary predefined) change in mass of different skeleton bones was found to correlate (r = 0.904) with position relatively the Earth's gravity vector. Vector dependence of bone loss ensues from local specificity of expression of bone metabolism genes which reflects mechanic prehistory of skeleton structures in the evolution of Homo erectus. Genetic polymorphism is accountable for high individual variability of bone loss attested by the dependence of bone loss rate on polymorphism of certain bone metabolism markers. Parameters of one and the other orbital vehicle did not modulate individual-specific stability of the bone loss ratio in different segments of the skeleton. This fact is considered as a phenotype fingerprint of local metabolism in the form of a locus-unique spatial structure of distribution of noncollagenous proteins responsible for position regulation of endosteal metabolism. Drug treatment of osteoporosis (n = 107) evidences that recovery rate depends on bone location; the most likely reason is different effectiveness of local osteotrophic intervention into areas of bustling resorption.

Clinical and serologic features of Lyme borreliosis in Russia.

OBJECTIVE: To describe clinical and serologic features of Lyme borreliosis, particularly the joint abnormalities, in Russian patients. METHODS: Physicians were invited to refer patients with past or present erythema migrans to the Rheumatology Institute in Moscow; field studies were done of residents in an area endemic for Lyme borreliosis, and a serosurvey was conducted of patients with nonspecific neurologic, cardiac, or joint symptoms. Serologic testing was done by ELISA and Western blotting using a strain of Borrelia afzelii, a member of the B. burgdorferi sensu lato complex, recovered from ticks from the field study site. RESULTS: Of 86 patients with erythema migrans, neurologic abnormalities developed in 26 (30%), cardiac involvement in 5 (6%), arthritis or arthralgia in 35 (41%), and acrodermatitis in 2 (2%). Joint involvement was usually characterized by one or a few brief episodes of joint swelling or pain in one large joint at a time. However, 69 of the 86 patients (80%) received antibiotic therapy early in the infection. The majority of patients with active infection had elevated levels of IgM or IgG antibody to B. afzelii by ELISA, and those with late infection often had IgG reactivity with > or = 5 spirochetal proteins, particularly the 37, 39, 41, 60, and 93 kDa antigens. In a serosurvey of 75 patients with facial palsy, atrioventricular block, or arthritis or arthralgia of uncertain cause, 6 had IgG reactivity with > or = 5 spirochetal proteins. CONCLUSION: Lyme borreliosis in Russia is similar to that in other parts of Europe. Brief episodes of arthritis or arthralgia were a common feature of the illness.

[The clinical and serological manifestations of Lyme disease in Russia]. / Klinicheskie i serologicheskie proiavleniia laimskoi bolezni v Rossii.

Out of 86 Lyme's disease patients with a history of migrating erythema nervous system, cardiovascular and articular involvement was observed in 27, 6 and 43% of cases. Acrodermatitis was diagnosed in 2% of patients. Affection of locomotor system manifested with acute arthritis episodes or pains in major joints. 11 patients of 12 examined at arthritis onset showed elevated titer of anti-Borrelia IgG antibodies. Serologically, of 80 patients with arthritis or arthralgia without prior migrating erythema 6 demonstrated antibodies to 5 and more Borrelia polypeptides.

[The clinical instrumental characteristics of the locomotor involvement in patients who have had Lyme disease]. / Kliniko-instrumental'naia kharakteristika porazheniia oporno-dvigatel'nogo apparata u bol'nykh, perenesshikh laimskuiu bolezn'.

Locomotor system has been studied in 24 patients with a history of Lyme's disease. All of them had arthralgia, 11 had relapsing arthritis, chronic arthritis occurred in 6 examinees. Arthritis presented as recurrent asymmetric mono-oligoarthritis affecting primarily joints of the lower limbs. Periarticular disorders were detected in 12 patients. Serologically, 18 of 24 patients had elevated titers of antibodies to Borrelia burgdorferi in indirect immunofluorescence test. Scintigraphy revealed polyarticular lesions in many cases, ultrasound investigation of the joints confirmed inflammatory nature of the pathological changes. It is inferred that combined methods of examination in diagnosis of Lyme's arthritis (titers to antibodies to Borrelia burgdorferi, ultrasound investigations, scintigraphy of the joints) provide most complete information.

[The humoral immunological response of patients with Lyme disease]. / Immunologicheskii gumoral'nyi otvet u bol'nykh laimskoi bolezn'iu.

Indirect immunofluorescence (II), enzyme-labelled antibodies (ELA), immune blotting (IB) were used for serological evaluation of 74 patients with Lyme disease living in the North-West and Central regions of Russia. Both acute and chronic borreliosis can be seropositive or seronegative. As shown by II and ELA, these patients had a moderate humoral response, high titers of the specific antibodies being a rare finding. The range of anti-Borrelia antibodies (ABA) identified by IB is limited and, as a rule, includes antibodies to no more than 5 proteins of Borrelia burgdorferi. The highest ABA levels were associated with locomotor lesions and were significantly greater of the above levels in patients with migrating erythema. Informative value of II and ELA in Lyme's disease diagnosis according to this study is equal because ELA is more sensitive, while II is more specific. They are both of little help in atypical borreliosis presentation. Most available of other adequate serological tests is IB.

[Antibodies to pathogens of Lyme's disease in patients with myocarditis and dilated cardiomyopathy]. / Antitela k vozbuditeliu bolezni Laima u bolnykh miokarditom i dilatatsionnoi kardiomiopatiei.

The paper presents the information on the involvement of the cardiovascular system in the patients with Lyme's disease as well as the results of serological investigation in patients with myocarditis and dilatation cardiomyopathy for the presence of antibodies to the causative agent of Lyme's disease with the aid of enzyme immunoassay. Out of 71 sera 3 specimens had the values of optical density higher than the upper normal limits. Based on the investigation conducted and the analysis of the clinical picture, the authors suspected a Borrelia origin of these cardiac involvements. However, to verify the diagnosis morphological examination of endomyocardiac biopsy specimens was found to be mandatory.

[The results of a clinico-serological examination of 60 patients with Lyme disease]. / Rezul'taty kliniko-serologicheskogo obsledovaniia 60 patsientov s laimskoi bolezn'iu.

Clinical and serological examinations were carried out in 60 patients with Lyme disease. The diagnosis was established on the basis of the disease marker--tick-borne migrating erythema and serological data obtained with the use of indirect immunofluorescence and Western blot. The spectrum of clinical manifestations and the rate of different clinical syndromes are described and compared with the data by this country and foreign authors. It is shown that Borrelia infection is capable of imitating rheumatic diseases.

[A description of a case of Lyme disease in eastern Siberia]. / Opisanie sluchaia bolezni Laima v Vostochnoi Sibiri.

A typical case of Lyme's borreliosis with classical stage course has been described in a 56-year-old male residing in Severobaikalsk. This case confirms the possibility of infestation with Lyme's disease in the regions where Ixodes ticks are widespread, as they are vectors of both tick-borne encephalitis virus and Lyme's borreliosis.

[A clinico-serological study of Lyme disease in the northwestern USSR]. / Kliniko-serologicheskoe izuchenie bolezni Laima v severo-zapade SSSR.

To reveal clinical signs and symptoms of Lyme's disease in the population of the endemic area, clinical and serological examinations of 416 persons have been performed. Preliminary screening, using indirect immunofluorescence, has revealed in 230 persons (group I) antibodies to the agent of the disease at a titre of greater than or equal to 1:20. Group II consisted of 186 patients who had not been serologically examined. Lyme's disease diagnosed in most cases by erythema annulare was found in 8 patients from group I and 12 patients from group II, all in all in 20 patients (4.8%) of all the patients examined. No typical late signs and symptoms of Lyme's disease have been observed. High antibody titres (greater than or equal to 1:80) were found in 24% of patients in group I and in 4.1% of patients in group II. Different clinical and immunological courses of borreliosis in the endemic area are discussed.