Лечение больных остеопорозом: вопросы длительности , приверженности и замены терапии

Osteoporosis is a chronic disease requiring long-term treatment aimed at reducing the risk of low-energy fractures, by improving the quality and strength of bones when taking this or that drug. Bisphosphonates (BPs) are deposited in the bone, so that they have an aftereffect. Due to the increased risk of adverse reactions with BPs, the author considers that the patients may take a drug holiday or be switched to alternative therapy. Denosumab may be used continuously for years and, unlike BPs, does not require discontinuation. It is effective in both untreated and already BP-treated patients. At the same time, when the treatment is discontinued, the effect of denosumab is reversible; therefore, oral BP or intravenous zoledronic acid is recommended to maintain the achieved effect.Остеопороз – хроническое заболевание, требующее длительного лечения, направленного на уменьшение риска низкоэнергетических переломов на фоне улучшения качества и прочности костей при приеме того или иного лекарственного средства. Бисфосфонаты (БФ) депонируются в кости, вследствие чего обладают эффектом последействия. В связи с увеличением риска нежелательных реакций на фоне приема БФ рассматривается возможность перевода пациентов на «лекарственные каникулы» или альтернативную терапию. Деносумаб может применяться непрерывно годами и в отличие от БФ не требует прекращения в лечении. Он эффективен как у не леченных ранее пациентов, так и у получавших ранее терапию БФ. В то же время при прекращении лечения действие деносумаба обратимо, поэтому для поддержания достигнутого эффекта рекомендуется прием пероральных БФ или внутривенное введение золедроновой кислоты

Роль витамина D в эффективности антирезорбтивной терапии

Vitamin D deficiency is one of the substantiated risk factors of osteoporosis. This vitamin is required to provide intestinal calcium absorption, bone metabolism regulation, and neuromuscular functions in the body. Vitamin D deficiency results in increased bone metabolism, causing bone loss progression and increasing the risk of fractures. Moreover, patients with vitamin D deficiency have a higher probability of fallings and loss of muscle mass, increasing in turn the risk of fractures. The combined formulation of alendronate and vitamin D as tablets is as effective as the mono-formulation of alendronate, but, furthermore, it has an additional advantage associated with the guaranteed vitamin D intake. At the same time the bioavailability of each component does not differ from the similar index when these agents are used alone.Дефицит витамина D - один из обоснованных факторов риска развития остеопороза. Этот витамин необходим для обеспечения абсорбции кальция в кишечнике и регуляции обменных процессов в костной ткани, а также для обеспечения нейромышечных функций в организме. Недостаточность витамина D приводит к повышению костного метаболизма, в результате чего прогрессирует потеря костной массы и увеличивается риск возникновения переломов. Кроме того, у пациентов с дефицитом витамина D существует более высокая вероятность падений и потери мышечной массы, что в свою очередь повышает риск возникновения переломов. Комбинированная таблетированная форма алендроната и витамина D так же эффективна, как и моноформа алендроната, но, кроме того, обладает дополнительным преимуществом, связанным с гарантированным поступлением в организм витамина D. При этом биодоступность каждого из компонентов не отличается от аналогичного показателя при индивидуальном их использовании

OSTEOPOROSIS: ASSESSMENT OF A RISK FOR RECURRENT LOW-TRAUMA FRACTURES IN POSTMENOPAUSAL WOMEN

Objective: to assess a risk for new fractures in a cohort of postmenopausal women who have sustained low-trauma fractures, by using the FRAX® algorithm, and to compare the assessments with data on the fractures have occurred during a prospective follow-up study.Subjects and methods. The investigation enrolled 128 postmenopausal women (mean age, 64.9±8.3 years) who had sustained low-trauma fractures at five sites (the hip, forearm, humeral neck, vertebral column, and ankle). A ten-year fracture risk was assessed using the FRAX® algorithm with and without regard for bone mineral density (BMD). New osteoporotic fractures were recorded during a three-year prospective follow-up study.Results and discussion. The average FRAX® algorithm values for all new osteoporotic and hip fractures in the entire group were 18.0±5.6 and 3.7±3.7% (without consideration of BMD), 17.9±6.6 and 3.5±4.0% (with consideration of BMD) (p > 0.05). The true incidence of recurrent fractures over 3 years was 17.2%. During 3 years, the incidence of recurrent fractures in the women who had sustained low-trauma fractures of the proximal hip, humeral neck, and spinal column was 28.6, 25.0, and 22.8%, respectively, which exceeded the estimated 10-year fracture risk for these sites. The history of multiple low-trauma fractures versus single one increased the risk for subsequent fractures by 3.63 and 9.43 times among women with high or low estimated FRAX risk rate, respectively.Conclusion. The three-year prospective follow-up study has shown that the FRAX® algorithm underestimated the risk associated with the presence of recurrent fractures in the history; moreover, new fractures significantly more commonly occur in persons who have sustained low-trauma fractures in the proximal hip, humoral neck, and vertebral column

TREATMENT OF OSTEOPOROSIS IN REAL CLINICAL PRACTICE: FREQUENCY OF PRESCRIPTIONS AND THERAPY ADHERENCE WITHIN THE FIRST YEAR AFTER OSTEOPOROTIC FRACTURE

Objective: to estimate the frequency of prescription for antiosteoporotic agents in real clinical practice and treatment adherence within a year after experienced low-trauma osteoporotic fracture (LOF). Subjects and methods. A questionnaire survey was made in 192 subjects aged over 50 years (mean age 66±8 years) who had sustained fractures at different sites after a fall from standing height. Therapy and its compliance were assessed 4 and 12 months after LOF. Results. One hundred and five (55%) patients received therapy, including 80 (73%) took only calcium preparations and vitamin D; 9 (8%), 15 (14%), and 5 (5%) patients had calcitonin, bisphosphonates, and strontium ranelate, respectively. At the same time, 87 (45%) subjects were given no antiosteoporotic drugs for a year after fracture. Throughout the follow-up, 42% of the respondents received treat- ment; 18% interrupted it within the first 4 months after fracture, and 40% started therapy 4 months or later (mean 6.5 months) after it. The reason for the absence of treatment was no recommendations by a traumatologist or primary care specialists in 49% of cases. Among those taking the drugs, treatment was recommended by the specialists of the Osteoporosis Center, Research Institute of Rheumatology, Russian Academy of Medical Sciences, in 89% of cases and by primary care specialists in only 11%.Conclusion. The study indicated that after LOF, the patients did not receive adequate antiosteoporotic therapy, at the same time 49% had no respective recommendations made by traumatologists or primary care physicians. The frequency of prescription for pathogenic agents for the treatment of osteoporosis was considerably increased during patient observation in a specialized osteoporosis center

The frequency of sarcopenia and factors affecting appendicular muscle mass in patients with systemic sclerosis

Aim. To determine the frequency of sarcopenia (SP) and to identify factors associated with the muscle mass in women with systemic sclerosis (SSc).Materials and methods. The study included 64 women with SSc aged 40–70 years. Questionnaires, clinical, instrumental, laboratory examinations and absorptiometry. Linear regression analysis was performed to identify factors associat ed with appendicular muscle mass (AMM).Results. Probable SP was detected in 35 (54.7 %), and confirmed SP – 17 (26.5 %) women with SSc. The frequency of SP did not differ depending on the form of the disease. Univariate linear analysis revealed the relationship between the AMM and BMI, nutritional status; mid-upper arm, waist, hip and calf circumferences, skin Rodnan score, cumulative dose of glucocorticoids (GC) and BMD of the proximal hip. Multivariate linear analysis confirmed the presence of associations between the AMM index and BMI (b = 0.65; p <0.001), the Rodnan skin score (b = –0.19; p = 0.047), the cumulative dose of GC (b = –0.22; p = 0.021).Conclusion. The study demonstrated that more than a quarter of patients with SSc had a confirmed SP. Although age is the main risk factor for SP in the general population, in our study it did not differ between patients with low and normal AMM. The cumulative dose of GC and the Rodnan skin score were negatively, and BMI was positively associated with the value of AMМ

Применение бисфосфонатов для лечения и профилактики остеопороза

Osteoporosis (OP) occupies one of the leading places in the structure of morbidity in people over 50 years of age, and its social significance is associated with the main complications – low-energy fractures of the vertebral bodies and bones of the peripheral skeleton, which lead to an increase in disability and mortality among the elderly, being a serious problem for public health. One of the doctor’s goals is the timely administration of anti-osteoporotic treatment. Bisphosphonates (BP) are first-line drugs for the treatment of OP. Since 1995, nitrogen-containing BPs have been widely used, they demonstrate their effect primarily by inhibiting the activity of osteoclasts and stimulating their apoptosis. The efficacy and safety of this class of drugs have been confirmed by numerous studies and many years of clinical practice. Since 2005, the production of generics of alendronic acid began, and later, after the patent protection of other BFs was closed, generics of risedronic, ibandronic and zoledronic acids appeared. In 2019, two domestic generics were registered – ibandronic acid 3 mg for intravenous (IV) injection once every 3 months (Rezoviva) and zoledronic acid 5 mg in 100 ml solution for IV injection once a year (Osteostatics). Since 2020 they have been introduced into clinical practice as part of import substitution, which increased the availability of these drugs and reduced the health care costs.Остеопороз (ОП) занимает одно из ведущих мест в структуре заболеваемости у лиц старше 50 лет, а его социальная значимость связана с основными осложнениями – низкоэнергетическими переломами тел позвонков и костей периферического скелета, которые приводят к росту инвалидности и смертности среди пожилого населения, являясь серьезной проблемой для общественного здравоохранения. Одной из задач, стоящих перед врачами, является своевременное назначение антиостеопоротического лечения. Бисфосфонаты (БФ) – препараты первой линии терапии ОП. С 1995 г. широко применяются азотсодержащие БФ, действие которых проявляется прежде всего за счет ингибирования активности остеокластов и стимулирования их апоптоза. Эффективность и безопасность данного класса препаратов подтверждены многочисленными исследованиями и многолетней клинической практикой. С 2005 г. начался выпуск дженериков алендроновой кислоты, а позднее, после закрытия патентной защиты других БФ, появились дженерики ризедроновой, ибандроновой и золедроновой кислот. В 2019 г. были зарегистрированы два отечественных дженерика – ибандроновая кислота 3 мг для внутривенного (в/в) введения 1 раз в 3 мес (Резовива) и золедроновая кислота 5 мг в 100 мл раствора для в/в капельного введения 1 раз в год (Остеостатикс), которые с 2020 г. в рамках импортозамещения стали внедряться в клиническую практику, что позволяет увеличить доступность данных лекарственных средств и снизить затраты системы здравоохранения

FARNESYL DIPHOSPHATE SYNTHASE (FDRS) AND GERANYLGERANYL DIPHOSPHATE SYNTHASE (GGSP1) GENE POLYMORPHISMS AND EFFICIENCY OF THERAPY WITH BISPHOSPHONATES IN RUSSIAN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS: A PILOT STUDY

Genetic factors that are an important hereditary component determining a predisposition to osteoporosis (OP) are 60–80% responsible for bone mineral density (BMD). Some polymorphic genes have been previously shown to affect the efficiency of performed anti-osteoporotic therapy.Objective: to study the impact of farnesyl diphosphate synthase (FDRS) and geranylgeranyl diphosphate synthase (GGSPI) gene polymorphisms on BMD changes during 12-month therapy with bisphosphonates (BP) in women with postmenopausal OP.Subjects and methods. The investigation enrolled 53 women with OP. Spine and proximal femur BMD was determined using X-ray densitometry before and after BP treatment. The -99A/C and -8188T ins/del polymorphisms in the FDPS and GGPS1 genes were investigated using real-time polymerase chain reaction.Results and discussion. The BMD changes were less marked in women with the C allele of C/T -99/C polymorphism in the FDPS gene than those in carriers of the genotype AA: 2.3±3.6 and 4.4±3.8% (р = 0.062) in the spine; 0.6±3.1 and 2.8±4.5% (р = 0.075) in the femoral neck; 0.5±2.9 and 2.5±2.8% (р = 0.020) in the entire femur, respectively. Femoral neck densitometry showed a significantly weaker response to BP treatment in the patients carrying the mutant genotype del/del of GGSP1 -8188T ins/del polymorphism than in those with the wild-type genotype ins/ins (0.8±4.2 and 4.1±2.5%, respectively; р = 0.030). No significant differences for this polymorphism were found in other areas of BMD measurement.Conclusion. The described pilot study has indicated that the examined FDPS and GGSP1 gene polymorphisms may be predictors for a response to BP therapy in patients with OP. Further investigations that will contribute to the choice of the most effective therapy for this disease are needed to confirm our results

Факторы риска и минеральная плотность кости в прогнозировании риска перелома у женщин в постменопаузе

The Russian model FRAX®, an algorithm for estimating the 10-year absolute risk of fractures, which is based on the identification of risk factors that increase fracture risk, was proposed in 2012 to detect people at high risk for fracture.Objective: to estimate the sensitivity and specificity of the Russian model FRAX® versus dual energy X-ray absorptiometry (DEXA) for predicting high fracture risk.Patients and methods. In 2013–2014, the FRAX® questionnaire was retrospectively filled in provided that all information was available in the initial documents on 224 women aged 50 years and older (mean age, 62±7 years), examined at the V.A. Nasonova Research Institute of Rheumatology in 2003–2004. The risk of major osteoporotic fractures was assessed in accordance with the guidelines of the Russian Osteoporosis Association both with and without regard for bone mineral density (BMD+/BMD-) in the femoral neck. The diagnosis of osteoporosis (OP) was based on the WHO criteria using DEXA values.Results. At a primary examination, 96 (43%) patients had a history of minimal trauma fractures, 105 (47%) had OP in the vertebral column and/or femoral neck; the FRAX® (BMD-) values higher than the therapeutic intervention threshold were seen in 70 (31%) patients. 71 (31%) women had no risk factors included in the FRAX® questionnaire. In accordance with the current guidelines, therapy should be recommended for 146 (65%) patients. Over the 10-year period, minimal trauma fractures occurred in 106 (47%) women, including in 46 (40%) of the 128 patients who had no history of fractures. The sensitivity of the FRAX® algorithm with BMD- and BMD+ was 41% (31–51%) and 38% (29–48%) and its specificity was 77% (68–84%) and 82% (74–88%), respectively. The area un-der the ROC curve (AUC) was 0.66 for FRAX® BMD- and 0.69 for FRAX® BMD+. The sensitivity of BMD values in the spine for predicting OP fractures was greater than that of the FRAX® algorithm and was as high as 53% (43–63%) with a lower specificity of 61% (52–70%) (AUC, 0.61) and these values in the femoral neck were as follows: a sensitivity of 25% (18–35%) with a specificity of 89% (82–94%) (AUC 0.64). Conclusion. The Russian model FRAX® for major OP fractures, which is calculated both with and without regard for BMD in the femoral neck, and DEXA fail to identify in full measure patients who need antiosteoporotic therapy, which calls for further investigations providing a pharmacoeconomic rationale for the application of these methods.Для выявления лиц, имеющих высокий риск перелома, в 2012 г. была предложена российская модель FRAX® – алгоритм оценки 10-летнего абсолютного риска переломов на основании определения факторов риска, повышающих вероятность возникновения перелома.Цель исследования – оценить чувствительность и специфичность российской модели FRAX® и рентгеновской денситометрии (DXA) для прогнозирования высокого риска перелома.Пациенты и методы. В 2013–2014 гг. на 224 женщины в возрасте 50 лет и старше (средний возраст – 62±7 лет), обследованные в 2003–2004 гг. в ФГБНУ НИИР им. В.А.Насоновой, ретроспективно заполнен вопросник FRAX® при условии наличия всей информации в первичной документации. Риск основных остеопоротических переломов (ОП-переломов) оценивался в соответствии с рекомендациями Российской ассоциации по остеопорозу как без, так и с учетом минеральной плотности кости (МПК-/МПК+) шейки бедра. Диагноз остеопороза (ОП) ставился на основании критериев ВОЗ при проведении DXA.Результаты. На момент первичного обследования переломы при минимальной травме в анамнезе имели 96 (43%) пациенток, ОП в позвоночнике и/или шейке бедра – 105 (47%), значения FRAX® (МПК-) выше порога терапевтического вмешательства – 70 (31%). У 71 (32%) женщины не было факторов риска, вносимых в вопросник FRAX®. В соответствии с современными рекомендациями терапию следовало назначить 146 (65%) пациенткам. За 10-летний период переломы при минимальном уровне травмы произошли у 106 (47%) женщин, в том числе у 46 (40%) из 128 пациенток, первоначально не имевших переломов. Чувствительность алгоритма FRAX® с МПК- и МПК+ составила 41% (31–51%) и 38% (29–48%), а специфичность – 77% (68–84%) и 82% (74–88%) соответственно; площадь под ROC-кривой (AUC) – 0,66 для FRAX® МПК- и 0,69 для FRAX® МПК+. Чувствительность значений МПК позвоночника для прогнозирования ОП-переломов была выше, чем алгоритма FRAX®, и достигала 53% (43–63%) при более низкой специфичности – 61% (52–70%; AUC 0,61), а для МПК шейки бедра эти параметры составили: чувствительность – 25% (18–35%) при специфичности 89% (82–94%; AUC 0,64).Выводы. Российская модель FRAX® для основных ОП-переломов, рассчитанная как без МПК шейки бедра, так и с ее учетом, и DXA не позволяют в полной мере выявлять пациентов, нуждающихся в назначении антиостеопоротической терапии, что требует проведения дальнейших исследований с фармакоэкономическим обоснованием использования этих методов