Indicators of the osteoclastogenesis system in men with different clinical types of ankylosing spondylitis

Objective: to evaluate the osteoclastogenesis regulatory system – osteoprotegerin/receptor activator of nuclear factor-κβ ligand (OPG/RANKL) system – in men with different clinical types of ankylosing spondylitis (AS).Subjects and methods. The osteoclastogenesis regulatory system was studied in 60 men, including 40 patients diagnosed with AS complying with the 1984 New York criteria and 20 men without AS. RANKL, a major stimulant of osteoclastogenesis, and OPG, a decoy receptor that binds RANKL and, accordingly, blocks osteoclastogenesis, were investigated.Results. It was shown that in the patients with AS, RANKL concentrations were normal and the content of OPG and OPG/RANKL ratio proved to be significantly higher than those in the men without AS. The highest OPG concentrations were recorded in patients with the axial form of this disease, its moderate activity and early X-ray stage. No relationship was found between the level of RANKL and the clinical characteristics of AS; however, there was a tendency to a slight increase in its concentration in patients with extraskeletal manifestations of AS, its high activity, high functional class, and late X-ray stage.Conclusion. The considerable increase in OPG levels and OPG/RANKL ratio was ascertained to be associated to the fact that 94% of the patients with late-stage AS characterized by the presence of numerous syndesmophytes. These changes must be compensatory in response to modestly increased RANKL level and enhanced bone resorption

Показатели системы остеокластогенеза у мужчин с различными клиническими вариантами анкилозирующего спондилита

Objective: to evaluate the osteoclastogenesis regulatory system – osteoprotegerin/receptor activator of nuclear factor-κβ ligand (OPG/RANKL) system – in men with different clinical types of ankylosing spondylitis (AS).Subjects and methods. The osteoclastogenesis regulatory system was studied in 60 men, including 40 patients diagnosed with AS complying with the 1984 New York criteria and 20 men without AS. RANKL, a major stimulant of osteoclastogenesis, and OPG, a decoy receptor that binds RANKL and, accordingly, blocks osteoclastogenesis, were investigated.Results. It was shown that in the patients with AS, RANKL concentrations were normal and the content of OPG and OPG/RANKL ratio proved to be significantly higher than those in the men without AS. The highest OPG concentrations were recorded in patients with the axial form of this disease, its moderate activity and early X-ray stage. No relationship was found between the level of RANKL and the clinical characteristics of AS; however, there was a tendency to a slight increase in its concentration in patients with extraskeletal manifestations of AS, its high activity, high functional class, and late X-ray stage.Conclusion. The considerable increase in OPG levels and OPG/RANKL ratio was ascertained to be associated to the fact that 94% of the patients with late-stage AS characterized by the presence of numerous syndesmophytes. These changes must be compensatory in response to modestly increased RANKL level and enhanced bone resorption.Цель исследования – оценить состояние системы регуляции остеокластогенеза – остеопротегерин/лиганд рецептора активатора нуклеарного фактора κβ (OPG/RANKL) – у мужчин с различными клиническими вариантами анкилозирующего спондилита (АС).Материал и методы. Система регуляции остеокластогенеза изучалась у 60 мужчин: 40 больных с диагнозом АС, соответствующим модифицированным Нью-Йоркским критериям (1984 г.) и 20 мужчин без АС. Исследовали RANKL – основной стимулятор остеокластогенеза и OPG – «рецептор-ловушку», связывающий RANKL и, соответственно, блокирующий остеокластогенез.Результаты исследования. Показано, что у больных АС концентрация RANKL была нормальной, а содержание OPG и отношение OPG/RANKL оказалось достоверно выше, чем у мужчин без АС. Наибольшая концентрация OPG зарегистрирована у пациентов с аксиальной формой заболевания, умеренной степенью активности и ранней рентгенологической стадией. Не выявлено зависимости уровня RANKL от клинических характеристик АС, однако отмечена тенденция к незначительному повышению его концентрации у пациентов с наличием внескелетных проявлений АС, высокой степенью активности, высоким функциональным классом и поздней рентгенологической стадией АС.Заключение. Установлено, что значительное повышение уровня OPG и отношения OPG/RANKL может быть связано с тем, что 94% пациентов имели позднюю стадию АС, характеризующуюся наличием множественных синдесмофитов. Данные изменения, вероятно, могут носить компенсаторный характер в ответ на незначительное повышение уровня RANKL и усиление костной резорбции

Динамика минеральной плотности кости на фоне 4-летней терапии ритуксимабом у женщин в постменопаузе, страдающих ревматоидным артритом

Objective: to estimate the time course of bone mineral density (BMD) changes during 4-year rituximab (RTM) therapy in postmenopausal women with rheumatoid arthritis (RA).Subjects and methods. Seventy-nine postmenopausal women with a valid diagnosis of RA were followed up. According to the basic therapy option, all the patients were allocated into two groups: 1) 44 patients who received combination therapy with RTM and methotrexate (MT); 2) 35 patients who had MT monotherapy. BMD was estimated by dual-energy X-ray absorptiometry using an Excell XR-46 stationary dualenergy X-ray bone densitometer (Norland, USA).Results. There was a statistically significant increase in femoral neck BMD and T score as compared to the baseline values in the RTM group after 3 years of follow-up. The MT monotherapy group showed no statistically significant densitometric changes in the femoral neck. The similar positive BMD changes were observed 4 years following RTM and MT therapy.Conclusion. Following 2 therapy cycles, femoral neck BMD parameters were noted to be stabilized in the patients with RA. After 3 therapy cycles, there was a positive densitometric change that remained by the fourth therapy cycle.Цель исследования – оценка динамики минеральной плотности кости (МПК) шейки бедра на фоне 4-летней терапии ритуксимабом (РТМ) у женщин в постменопаузе, страдающих ревматоидным артритом (РА).Материал и методы. Под наблюдением находилось 79 женщин в постменопаузе с достоверным диагнозом РА. Все больные были распределены в две группы в зависимости от варианта базисной терапии: 1-я группа (n=44) получала комбинированную терапию РТМ и метотрексатом (МТ); 2-я группа (n=35) – монотерапию МТ. МПК определяли методом двухэнергетической рентгеновской абсорбциометрии с помощью стационарного двухэнергетического рентгеновского костного денситометра Exceell XR-46 (Norland, США).Результаты. Установлено статистически значимое повышение показателей МПК и Т-критерия шейки бедра по сравнению с исходными показателями через 3 года наблюдения в группе больных, получавших РТМ. В группе пациенток, получавших монотерапию МТ, статистически значимого изменения денситометрических показателей шейки бедра не отмечено. Аналогичная положительная динамика МПК наблюдалась через 4 года терапии РТМ и МТ.Выводы. После 2 курсов терапии отмечена стабилизация показателей МПК шейки бедра у больных РА. После 3 курсов лечения определялась положительная динамика денситометрических показателей, которая сохранялась и к 4-му курсу терапии

Time course of bone mineral density changes during 4-year rituximab therapy in postmenopausal women with rheumatoid arthritis

Objective: to estimate the time course of bone mineral density (BMD) changes during 4-year rituximab (RTM) therapy in postmenopausal women with rheumatoid arthritis (RA).Subjects and methods. Seventy-nine postmenopausal women with a valid diagnosis of RA were followed up. According to the basic therapy option, all the patients were allocated into two groups: 1) 44 patients who received combination therapy with RTM and methotrexate (MT); 2) 35 patients who had MT monotherapy. BMD was estimated by dual-energy X-ray absorptiometry using an Excell XR-46 stationary dualenergy X-ray bone densitometer (Norland, USA).Results. There was a statistically significant increase in femoral neck BMD and T score as compared to the baseline values in the RTM group after 3 years of follow-up. The MT monotherapy group showed no statistically significant densitometric changes in the femoral neck. The similar positive BMD changes were observed 4 years following RTM and MT therapy.Conclusion. Following 2 therapy cycles, femoral neck BMD parameters were noted to be stabilized in the patients with RA. After 3 therapy cycles, there was a positive densitometric change that remained by the fourth therapy cycle

Clinical management of cutaneous adverse events in patients on targeted anticancer therapies and immunotherapies: a national consensus statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology

Progress in the understanding of many tumors has enabled the development of new therapies, such as those targeted at specific molecules involved in cell growth (targeted therapies) or intended to modulate the immune system (immunotherapy). However, along with the clinical benefit provided by these new treatments, new adverse effects have also appeared. Dermatological toxicities such as papulopustular eruptions, xerosis, and pruritus are common with EGFR inhibitors. Other adverse effects have also been described with PDGFR, BCR-ABL, and MAPK tyrosine kinase inhibitors, antiangiogenic drugs, and inhibitors at immune checkpoints such as CTLA-4 and PD-1/PD-L1. Onset of these adverse effects often causes dose reductions and/or delays in administering the prescribed therapy, which can affect patient survival and quality of life. It is, therefore, important to prevent the occurrence of these adverse effects, or to treat unavoidable ones as soon as possible. This requires cooperation between medical oncologists and dermatologists. This article reviews the various dermatological toxicities associated with targeted therapies and immunotherapies, along with their diagnosis and therapeutic management