scholarly journals ANABOLIChESKAYa TERAPIYa OSTEOPOROZA.TERIPAPARATID: EFFEKTIVNOST', BEZOPASNOST' I OBLAST' PRIMENENIYa

2013 ◽  
Vol 16 (2) ◽  
pp. 32-40
Author(s):  
Zh E BELAYa ◽  
L Ya ROZhINSKAYa
Keyword(s):  
Bone Formation ◽  
Bone Remodeling ◽  
Vertebral Fractures ◽  
Previous Treatment ◽  
Fragility Fractures ◽  
Bone Modeling ◽  
Severe Osteoporosis ◽  
Subcutaneous Injections ◽  
Acid Fragment ◽  
History Of

This review of the literature has been dedicated to experimental and clinical studies of mechanism of action and efficacy of 1—34 amino acid fragment of parathyroid hormone — teriparatide as well as others contries experience of its prescribtion. Teriparatide is an osteoanabolic agent which stimulates bone formation by affecting bone modeling and by stimulating bone remodeling. The effects on modeling lead to increased bone formation whereas the effects on bone remodeling lead to increased bone turnover. Thus, in its mode of action teriparatide differs from all others medicines currently available to treat osteoporosis. Daily subcutaneous injections of teriparatide are proved to be effective to prevent low-traumatic vertebral and non-vertebral fractures in postmenopausal women with the history of vertebral fractures. Teriparatide is effective to treat osteoporosis in male and even more effective than alendronate to treat glucocorticoid-induced osteoporosis. Due to high cost and some restriction related to the duration of therapy (up to 18 months in Russia and 24 months in others countries) teriparatide should be recommended to treat severe osteoporosis in patients with a history >1 moderate clinical vertebral fracture or two or more vertebral fragility fractures or in case the previous treatment was not effective. Teriparatide should be prescribed after bisphosphonates or other antiosteoporotic treatment, but not in the combination with bisphosphonates. The prescribtion of bisphosphonates after teriparatide is effective to maintaine and further improve the effect. Thus, teriparatide is effective to treat severe osteoporosis and osteoporosis resistant to other therapy.

scholarly journals Anti-Sclerostin Antibodies in Osteoporosis and Other Bone Diseases

2020 ◽  
Vol 9 (11) ◽  
pp. 3439
Author(s):  
Stéphanie Fabre ◽  
Thomas Funck-Brentano ◽  
Martine Cohen-Solal
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Postmenopausal Women ◽  
Bone Remodeling ◽  
Wnt Pathway ◽  
Human Monoclonal Antibody ◽  
Bone Diseases ◽  
Mineral Density ◽  
High Fracture ◽  
History Of

The Wnt pathway is a key element of bone remodeling; its activation stimulates bone formation and inhibits bone resorption. The discovery of sclerostin, a natural antagonist of the Wnt pathway, promoted the development of romosozumab, a human monoclonal antibody directed against sclerostin, as well as other anti-sclerostin antibodies. Phase 3 studies have shown the efficacy of romosozumab in the prevention of fractures in postmenopausal women, against placebo but also against alendronate or teriparatide and this treatment also allows bone mineral density (BMD) increase in men. Romosozumab induces the uncoupling of bone remodeling, leading to both an increase in bone formation and a decrease in bone resorption during the first months of treatment. The effect is attenuated over time and reversible when stopped but transition with anti-resorbing agents allows the maintenance or reinforcement of BMD improvements. Some concerns were raised about cardiovascular events. Therefore, romosozumab was recently approved in several countries for the treatment of severe osteoporosis in postmenopausal women with high fracture risk and without a history of heart attack, myocardial infarction or stroke. This review aims to outline the role of sclerostin, the efficacy and safety of anti-sclerostin therapies and in particular romosozumab and their place in therapeutic strategies against osteoporosis or other bone diseases.

scholarly journals Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis

2016 ◽  
Vol 8 (6) ◽  
pp. 225-235 ◽  
Author(s):  
Bente Langdahl ◽  
Serge Ferrari ◽  
David W. Dempster
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
De Novo ◽  
Skeletal Development ◽  
Cathepsin K ◽  
Bone Modeling ◽  
Treatment Of Osteoporosis ◽  
Age Related

The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20–30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that rediscovering a phenomenon that was first observed more half a century ago will have an important impact on our understanding of how new antifracture treatments work.

scholarly journals Teriparatide as option for severe osteoporosis

2016 ◽  
Vol 11 (4) ◽  
pp. 348-354
Author(s):  
Mara CARSOTE ◽  
◽  
Adina GHEMIGIAN ◽  
Otilia RADU ◽  
Ana VALEA ◽  
...  
Keyword(s):  
Fragility Fractures ◽  
Original Study ◽  
Male Hypogonadism ◽  
Mineral Density ◽  
Severe Osteoporosis ◽  
Prior Therapy ◽  
End Point ◽  
High Bone ◽  
History Of ◽  
Anabolic Window

e introduce an original study referring to Romanian population treated with teriparatide (TPT), an anabolic drug for severe menopausal, glucocorticoid and male hypogonadism-related osteoporosis. Primary end point is to analyze the parameters of persons who fulfilled the national criteria of TPT regarding co-morbidities and bone profile. Secondary end point is to reveal the skeleton indices 12 months after TPT (20 μg/day subcutaneous). Informed written consent was signed between July 2015 and June 2016. Out of 21 patients with a mean age of 66.76 years (yrs), except for 2 men, there were menopausal females with av. 21.47 yrs since menopause. 57% had a history of superior digestive condition, another 57% had a chronic thyroid disease and 29% had a non-thyroid autoimmune morbidity. 17 patients were pre-exposed to anti-osteoporotic drugs 4.23+/-3.49 yrs. Number of prevalent fractures was: 3.75+/-2.17 (median 3; min 1, max 9). 42% (N=9) of subjects were followed for 1 year: no new fracture was registered; each patient had at least one DXA site with a BMD (Bone Mineral Density) increase (mean T-score increase of the most affected region was of 0.56+/-0.2 SD); osteocalcin statistically significant elevated from 18.87+/4.22 ng/mL to 42.8+/-16.3 ng/mL (p<0.0005) while CrossLaps went from 0.46+/-0.22 ng/mL to 0.65+/-0.3 ng/mL (p=0.15). Early drop-offs were registered in 2 patients. Based on this original study, patients with severe osteoporosis having a burden of many years of prior therapy or fragility fractures became candidates for TPT. After 12 months, the anabolic window was revealed by high bone remodelling blood markers, especially for osteocalcin.

scholarly journals Comparative efficacy and safety of alendronate and teriparatide in bone loss reduction and prevention of vertebral fracture in osteoporotic Chinese patients

2021 ◽  
Vol 20 (10) ◽  
pp. 2199-2204
Author(s):  
Yujun Qi ◽  
Wenyuan Wang ◽  
Wenlin Sun ◽  
Qiuyin Pan
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Loss ◽  
Bone Formation ◽  
Fragility Fractures ◽  
Bone Alkaline Phosphatase ◽  
Chinese Patients ◽  
Fracture Rate ◽  
Efficacy And Safety ◽  
Mineral Density ◽  
History Of

Purpose: To compare the effect of teriparatide and alendronate (bisphosphonate, BPP) among Chinese patients with osteoporosis (OoP).Method: Chinese subjects aged > 40 years with a history of vertebral/non-vertebral osteoporotic fragility/fractures were enrolled, and administered either teriparatide (TPT 20 μg/day) subcutaneously or alendronate (BPP)10 mg orally once daily for 12 months. Bone mineral density (BMD), measured using x-ray techniques, and bone formation biomarkers such as osteocalcin [OTC] and bone alkaline phosphatase, were assessed at baseline, and after 6 and 12 months of treatment. The proportion of patients with fractures as well as fracture rate were also recorded. The safety of the drugs was evaluated based treatment emergent adverse events.Result: In Chinese men with OoP, substantially greater improvement in BMD was observed in TPT group, compared to BPP group. TPT demonstrated substantially greater improvement in OTC and, bone alkaline phosphatase than in BPP. Also, patients treated with TPT had significantly lower incidence of new fracture than BPP group during the study period, irrespective of gender distribution (relative risk reduction at 6 and 12 months was 45 and 47 % respectively). The results showed that TPT was superior to BPP in increasing BMD and bone formation biomarkers and reducing new fractures in both male and female patients with osteoporosis.Conclusion: Teriparatide is effective and safe in reducing bone loss and preventing vertebral fractures in Chinese patients with osteoporosis. Furthermore, the results show that there is no gender difference in the efficacy and safety of teriparatide in osteoporosis.

Gene mutation and drug resistance of M. tuberculosis in the patients followed up in the city of Moscow

2020 ◽  
Vol 97 (12) ◽  
pp. 34-44
Author(s):  
M. A. Krasnova ◽  
E. M. Belilovsky ◽  
S. E. Borisov ◽  
A. A. Khakhalina ◽  
Yu. D. Mikhaylova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Statistical Significance ◽  
Molecular Genetic ◽  
Previous Treatment ◽  
Repeated Treatment ◽  
Phenotypic Resistance ◽  
Therapy Regimen ◽  
Treatment History ◽  
History Of ◽  
Relationship Of

The article describes a retrospective study of the results of microbiological and molecular genetic tests of 685 M. tuberculosis cultures isolated from 685 adult tuberculosis patients registered for dispensary follow-up in Moscow in 2014.The following was identified during the study: phenotypic drug resistance (FDR) of MTB to rifampicin, isoniazid, fluoroquinolones, kanamycin, amikacin, and capreomycin in groups of patients with different treatment history; the frequency of FDR to the above anti-tuberculosis drugs in strains with mutations being drug resistance markers; the frequency of various mutations in case of FDR of mycobacteria in the patients from different groups; the relationship of FDR or the presence of a particular mutation with various characteristics of the patients and their treatment history.The history of previous treatment was determined as statistical significance to provide the greatest influence on the spread of drug resistant MTB: patients undergoing repeated treatment had FDR more often and also a much more pronounced variety of mutations being markers of FDR to certain anti-tuberculosis drugs.The results of the study showed that the detection of genetic mutations in MBT associated with FDR was a reliable tool for predicting phenotypic resistance and should be used as the main method for selecting anti-tuberculosis drugs when compiling the etiotropic therapy regimen.

scholarly journals The Development of Molecular Biology of Osteoporosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia
Keyword(s):  
Bone Resorption ◽  
Molecular Biology ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Cell Activity ◽  
Bone Cell ◽  
Bone Disorders ◽  
Molecular Aspects

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

scholarly journals Vertebral Fractures in Ireland: A Sub-analysis of the DXA HIP Project

2021 ◽  
Author(s):  
John J Carey ◽  
Lan Yang ◽  
E. Erjiang ◽  
Tingyan Wang ◽  
Kelly Gorham ◽  
...  
Keyword(s):  
Hip Fracture ◽  
High Risk ◽  
Vertebral Fractures ◽  
Fragility Fractures ◽  
Vertebral Fracture Assessment ◽  
International Studies ◽  
Men And Women ◽  
Women Subjects ◽  
The World ◽  
High Risk Populations

AbstractOsteoporosis is an important global health problem resulting in fragility fractures. The vertebrae are the commonest site of fracture resulting in extreme illness burden, and having the highest associated mortality. International studies show that vertebral fractures (VF) increase in prevalence with age, similarly in men and women, but differ across different regions of the world. Ireland has one of the highest rates of hip fracture in the world but data on vertebral fractures are limited. In this study we examined the prevalence of VF and associated major risk factors, using a sample of subjects who underwent vertebral fracture assessment (VFA) performed on 2 dual-energy X-ray absorptiometry (DXA) machines. A total of 1296 subjects aged 40 years and older had a valid VFA report and DXA information available, including 254 men and 1042 women. Subjects had a mean age of 70 years, 805 (62%) had prior fractures, mean spine T-score was − 1.4 and mean total hip T-scores was − 1.2, while mean FRAX scores were 15.4% and 4.8% for major osteoporotic fracture and hip fracture, respectively. Although 95 (7%) had a known VF prior to scanning, 283 (22%) patients had at least 1 VF on their scan: 161 had 1, 61 had 2, and 61 had 3 or more. The prevalence of VF increased with age from 11.5% in those aged 40–49 years to > 33% among those aged ≥ 80 years. Both men and women with VF had significantly lower BMD at each measured site, and significantly higher FRAX scores, P < 0.01. These data suggest VF are common in high risk populations, particularly older men and women with low BMD, previous fractures, and at high risk of fracture. Urgent attention is needed to examine effective ways to identify those at risk and to reduce the burden of VF.

scholarly journals THE EFFECT OF ADMINISTRATION OF EPINEPHRINE ON THE LEUKOCYTE COUNTS OF NORMAL SUBJECTS

Blood ◽  
1950 ◽  
Vol 5 (8) ◽  
pp. 723-731 ◽  
Author(s):  
COLIN WHITE ◽  
TSUIN HWA LING ◽  
ARNOLD M. KLEIN
Keyword(s):  
Eosinophil Count ◽  
Adrenocorticotropic Hormone ◽  
Leukocyte Count ◽  
Normal Subjects ◽  
Total Count ◽  
Subcutaneous Injections ◽  
History Of ◽  
Leukocyte Counts ◽  
Adrenocortical Hormone ◽  
The One

Abstract 1. Thirty-seven normal subjects were given subcutaneous injections of epinephrine, ranging from 0.25 to 0.5 mg., and the effects on the leukocytes were noted. 2. The neutrophils rose steadily for the three and one-half hours during which blood counts were made. The small lymphocytes rose in the first half hour, then fell below normal and finally returned towards normal. The eosinophils rose at first and then fell below normal for the remainder of the period. 3. The three doses of epinephrine used produced effects which differed quantitatively but not qualitatively. The most readily identified effect of the smallest dose was the one-half hour rise in lymphocytes or the one-half hour rise in total count. A dose of 0.5 mg. is satisfactory for work of this kind. 4. Subjects with a history of allergy showed a greater tendency than the remainder to exhibit a one-half hour rise in the eosinophil count. 5. The changes in the leukocyte count produced by epinephrine are similar to, but not identical with, those produced by adrenocortical hormone or adrenocorticotropic hormone.

scholarly journals Risk factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil

2017 ◽  
Vol 51 (0) ◽  
Author(s):  
Geisa Fregona ◽  
Lorrayne Belique Cosme ◽  
Cláudia Maria Marques Moreira ◽  
José Luis Bussular ◽  
Valdério do Valle Dettoni ◽  
...  
Keyword(s):  
Previous Treatment ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Espírito Santo ◽  
Factors Associated ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
History Of ◽  
Espirito Santo

ABSTRACT OBJECTIVE To analyze the prevalence and factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil. METHODS This is a cross-sectional study of cases of tuberculosis tested for first-line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin) in Espírito Santo between 2002 and 2012. We have used laboratory data and registration of cases of tuberculosis – from the Sistema Nacional de Agravos de Notificação and Sistema para Tratamentos Especiais de Tuberculose. Individuals have been classified as resistant and non-resistant and compared in relation to the sociodemographic, clinical, and epidemiological variables. Some variables have been included in a logistic regression model to establish the factors associated with resistance. RESULTS In the study period, 1,669 individuals underwent anti-tuberculosis drug susceptibility testing. Of these individuals, 10.6% showed resistance to any anti-tuberculosis drug. The rate of multidrug resistance observed, that is, to rifampicin and isoniazid, has been 5%. After multiple analysis, we have identified as independent factors associated with resistant tuberculosis: history of previous treatment of tuberculosis [recurrence (OR = 7.72; 95%CI 4.24–14.05) and re-entry after abandonment (OR = 3.91; 95%CI 1.81–8.43)], smoking (OR = 3.93; 95%CI 1.98–7.79), and positive culture for Mycobacterium tuberculosis at the time of notification of the case (OR = 3.22; 95%CI 1.15–8.99). CONCLUSIONS The partnership between tuberculosis control programs and health teams working in the network of Primary Health Care needs to be strengthened. This would allow the identification and monitoring of individuals with a history of previous treatment of tuberculosis and smoking. Moreover, the expansion of the offer of the culture of tuberculosis and anti-tuberculosis drug susceptibility testing would provide greater diagnostic capacity for the resistant types in Espírito Santo.

Absence of bone remodeling compartment canopies correlates with deficient bone formation in post-menopausal women

Bone ◽  
2010 ◽  
Vol 46 ◽  
pp. S67-S68
Author(s):  
Thomas Andersen ◽  
Ellen Hauge ◽  
Jens Bollerslev ◽  
Jean-Marie Delaisse
Keyword(s):  
Bone Formation ◽  
Bone Remodeling ◽  
Menopausal Women ◽  
Post Menopausal
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