Osteoprotective properties of a combination of HDBA complex and vitamins D3 and B6 (Osteo-Vit D3)

Остеопротекторные свойства комбинации HDBA комплекса с витаминами D₃ и B₆ («Остео-Вит D₃)

В.И. Струков¹, Е.В. Петрова², П.А. Полубояринов³, Н.В. Еремина¹, А.В. Котовский¹, Р.Т. Галеева¹, Л.Г. Радченко¹, И.А. Самылина⁴

¹  Пензенский институт усовершенствования врачей – филиал Федерального государственного бюджетного образовательного учреждения дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации (ПИУВ – филиал ФГБОУ ДПО РМАНПО Минздрава России); Российская Федерация , 440060, г. Пенза, ул. Стасова, 8А.

² Пензенский государственный университет;

Российская Федерация, 440026, г. Пенза, ул. Красная, 40

³ Федеральное государственное бюджетное образовательное учреждение высшего образования «Пензенский государственный университет архитектуры и строительства» (ФГБОУ ВО ПГУАС); Российская Федерация. 440028, г. Пенза, ул. Германа Титова, 28.

⁴ Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет);

Российская Федерация. 119991 Москва, ул. Большая Пироговская, д. 2–4

 

 

СВЕДЕНИЯ ОБ АВТОРАХ

Струков Виллорий Иванович – профессор кафедры педиатрии и неонатологии ПИУВ – филиала ФГБОУ ДПО РМАНПО Минздрава России, доктор медицинских наук, профессор. Тел.: +7 (965) 633-60-40. E-mail: villor3737@yandex.ru

Еремина Наталья Вячеславовна – заведующая кафедрой стоматологии общей практики, стоматологии терапевтической и стоматологии детской ПИУВ – филиала ФГБОУ ДПО РМАНПО Минздрава России, доктор медицинских наук, профессор. Тел.: +7 (902) 204-19-99. E-mail: ereminanat@gmail.com

Петрова Елена Владимировна – заведующая кафедрой «Неврология, нейрохирургия и психиатрия» Медицинского института ФГБОУ ВО «Пензенский государственный университет», доцент,  кандидат медицинских наук, Тел: +7 (927) 289-66-86 . E-mail:  petrovaelena2010@yandex.ru

Полубояринов Павел Аркадьевич – кандидат сельскохозяйственных наук, доцент, заведующий кафедрой «Инженерная экология» ФГБОУ ВО «Пензенский государственный университет архитектуры и строительства» Тел: +7 (950) 230-48-76. E-mail:  79502304876@yandex.ru

Котовский Александр Валерьевич – доцент кафедры педиатрии и неонатологии ПИУВ – филиала ФГБОУ ДПО РМАНПО Минздрава России, кандидат медицинских наук, доцент. Тел.: +7 (927) 361-16-54. E-mail: kotovskij@list.ru

Галеева Рамзия Тимуршовна – доцент кафедры педиатрии и неонатологии ПИУВ – филиала ФГБОУ ДПО РМАНПО Минздрава России, кандидат медицинских наук, доцент. Тел.: +7 (927) 289-89-04. E-mail: rtgaleeva@gmail.com

Радченко Лариса Григорьевна – доцент кафедры педиатрии и неонатологии ПИУВ – филиала ФГБОУ ДПО РМАНПО Минздрава России, кандидат медицинских наук, доцент. Тел.: +7 (987) 516-35-74. E-mail: lararad2012@yandex.ru

И.А. Самылина – доктор фармацевтических наук, член-корреспондент РАН, профессор кафедры фармацевтического естествознания Первого Московского государственного медицинского университета им. И.М. Сеченова Минздрава России. Teл.: +7 (916) 585-42-17. E-mail:laznata@mail.ru

 

РЕЗЮМЕ

Прием ряда лекарственных препаратов (в том числе антибиотиков) сопровождается повышением риска возникновения переломов, развития воспалительных заболеваний суставов, нарушений в работе иммунной и кроветворной систем. Поэтому особенно актуально применение препаратов, обладающих способностью нивелировать негативное влияние различных лекарственных средств (ЛС) на опорно-двигательный аппарат и безопасно восстанавливать прочность костной ткани у лиц разных возрастных категорий. Такими свойствами характеризуется отечественный препарат класса остеобиотиков «Остео-Вит D₃», прием которого рекомендуется сочетать с антибиотикотерапией. Доказана его способность нейтрализовывать негативное влияние различных ЛС на опорно-двигательный аппарат и безопасно восстанавливать прочность костной ткани у пациентов любого возраста. Немаловажно, что действие «Остео-Вита D₃» основано на активации собственных резервов организма. Препарат не содержит кальция, поскольку давно установлено, что переломы случаются не по причине дефицита минерала, а из-за нарушения его обмена. Активные действующие компоненты остеобиотика «Остео-Вит D₃»: HDBA органик комплекс (трутневый гомогенат), оказывающий выраженное гонадотропное действие и стимулирующий выработку эндогенного тестостерона, что способствует восстановлению гормонального баланса, выработке коллагена; витамин D₃, позволяющий задействовать для повышения минеральной плотности костной ткани (МПКТ) собственные кальциевые резервы организма, а также витамин В₆, способствующий снижению уровня гомоцистеина в плазме крови. Синергическое действие названных веществ обеспечивает восстановление нарушенного метаболизма кальция в организме, а также и его удержание в костной ткани. Протекторный эффект остеобиотика распространяется также на иммунную и кроветворные системы. «Остео-Вит D₃» положительно влияет на механизмы как врожденного, так и приобретенного иммунитета, поддерживая нормальное функционирование иммунной системы, улучшает гемопоэз. Если избежать антибиотикотерапии нельзя, остеобиотик защитит органы и ткани от ее разрушительного влияния, снизит количество побочных эффектов.

Ключевые слова: Остео-Вит D₃, остеобиотик, антибиотики

Для цитирования: Струков В.И., Петрова Е.В., Полубояринов П.А., Еремина Н.В., Котовский А.В., Галеева Р.Т., Радченко Л.Г., Самылина И.А. Остеопротекторные свойства комбинации HDBA комплекса с витаминами D₃ и B₆ (Остео-Вит D₃). Фармация, 2020; 70 (1): https://doi.org/10/29296/25419218-2020-01-

 

 

Osteoprotective properties of a combination of HDBA complex and vitamins D₃ and B₆ (Osteo-Vit D₃)

V.I. Strukov, E.V. Petrova, P.A. Poluboyarinov, N.V. Eremina, A.V. Kotovsky, R.T. Galeeva, L.G. Radchenko, I.A. Samylina

Farmatsiya (Pharmacy), 2020

 

INFORMATION ABOUT THE AUTHORS

Strukov Villory Ivanovich – Doctor of Medical Sciences, Professor, Department of Pediatrics and Neonatology of Penza State Institute for Postgraduate Medical Training. Phone: +7 (965) 633-60-40. E-mail: villor3737@yandex.ru.

Eremina Natalia Viacheslavovna – Doctor of Medical Sciences, Professor, Head of Department of General Practice Dentistry, Therapeutic Dentistry and Pediatric Dentistry of Penza State Institute for Postgraduate Medical Training. Phone: +7 (902) 204-19-99. E-mail: ereminanat@gmail.com.

Petrova Elena Vladimirovna – PhD, Associate professor, Head of Department of Neurology, Neurosurgery and Psychiatry, Penza State University, 40, Krasnaya Street, Penza, 440026, Russia. Tel.: +7 (927) 289-66-86, E-mail: petrovaelena2010@yandex.ru.

Poluboyarinov Pavel Vladimirovich – Candidate of Agricultural Sciences, Associate Professor, Head of the Department “Environmental Engineering”, Penza State University for Architecture and Construction. Phone: +7 (950) 230-48-76. E-mail:  79502304876@yandex.ru.

Kotovsky Aleksandr Viktorovich – Candidate of Medical Sciences, Associate Professor, Department of Pediatrics and Neonatology of Penza State Institute for Postgraduate Medical Training. Phone: +7 (927) 361-16-54. E-mail: kotovskij@list.ru.

Galeeva Ramziya Timurovna – Cancidate of Medical Sciences, Associate Professor, Department of Pediatrics and Neonatology of Penza State Institute for Postgraduate Medical Training. Phone: +7 (927) 289-89-04. E-mail: rtgaleeva@gmail.com.

Radchenko Larisa Grigorievna – Cancicate of Medical Sciences, Associate Professor, Department of Pediatrics and Neonatology of Penza State Institute for Postgraduate Medical Training. Phone: +7 (987) 516-35-74. E-mail: lararad2012@yandex.ru.

Samylina Irina Alexandrovna – doctor of pharmaceutical sciences, corresponding member of the RAS, professor of the Pharmaceutical Natural Sciences Department at Sechenov University; Tel.: +7 (916) 585-42-17. E-mail:laznata@mail.ru.

 

SUMMARY

The use of a number of drugs (including antibiotics) is accompanied by a higher risk of fractures, by the development of inflammatory joint diseases, and malfunctions of the immune and hematopoietic systems. Therefore, it is relevant to take drugs that are able to neutralize the negative effects of various drugs on the locomotor system and to safely restore bone strength in people of different age groups. These properties are available in the Russian osteobiotic Osteo-Vit D₃, the intake of which is recommended to be combined with antibiotic therapy. There is evidence that the drug is able to neutralize the negative effects of various agents on the locomotor system and to safely restore bone strength in patients of any age. It is also important that the action of Osteo-Vit D₃ is based on the activation of the body’s own reserves. The drug does not contain calcium, since it has long been established that fractures occur due to impaired metabolism of the mineral rather than its deficiency. The active ingredients of the osteobiotic Osteo-Vit D₃, such as the HDBA organic complex (drone homogenate) that has a pronounced gonadotropic activity and stimulates endogenous testosterone, which contributes to hormonal balance restoration and collagen production; vitamin D₃ that is able to set in motion the body’s own calcium reserves to increase bone mineral density; and vitamin B₆ that can lower plasma homocysteine levels. The synergistic activity of these substances restores the body’s impaired metabolism of calcium, as well as its bone tissue retention. The protective effect of the osteobiotic also extends to the immune and hematopoietic systems. Osteo-Vit D₃ positively affects the mechanisms of both innate and acquired immunity, supporting the normal functioning of the immune system, and improves hematopoiesis. If antibiotic therapy cannot be avoided, the osteobiotic will protect organs and tissues from this therapy and reduce the number of adverse reactions.

Key words: Osteo-Vit D₃, osteobiotic, antibiotics.

For citation: Strukov V.I., Petrova E.V., Poluboyarinov P.A., Eremina N.V., Kotovsky A.V., Galeeva R.T., Radchenko L.G., Samylina I.A. Osteoprotective properties of a combination of HDBA complex and vitamins D₃ and B₆ (Osteo-Vit D₃).  Farmatsiya (Pharmacy), 2020; 70 (1). https://doi.org/10/29296/25419218-2020-01-

 

The incidence of fractures in Russia and in the world has become almost an epidemic, and fractures are getting “younger”. For instance, until the 90s of the last century spinal fractures in childhood were considered as extremely rare. The analysis of injury statistics for the recent years showed a significant increase (by 9.6%) in this indicator. There is an increase in the number of recurrent fractures, the consolidation of which requires more time. Especially it concerns children.

This state of things has several reasons, particularly, widespread use of some groups of medicaments. A number of drugs have a negative effect on bone metabolism. First of all, these are glucocorticoids, proton pump inhibitors, selective serotonin reuptake inhibitors, thiazolidinediones, anticonvulsants, medroxyprogesterone acetate, hormone deprivation therapy drugs, calcineurin inhibitors, anticoagulants, chemotherapy drugs. Recent studies have proven the negative effect of antibiotic therapy on bone metabolism.

The widespread use of antimicrobial medicaments over the last 80 years saved millions of human lives. Many diseases caused by pathogenic and commensal microorganisms were defeated. However, the abuse of drugs of the said group negatively affects the state of the human body. The immunomodulatory effect of indigenous intestinal microbiota is proven to affect not only gastrointestinal tract, but also the state of liver, brain, heart, and skeleton.

According to the results of numerous studies, the destruction of intestinal microbiota when taking antibiotics causes an anti-inflammatory response of the immune system. The latter contributes to the suppression of osteoblast-mediated bone formation and/or enhanced osteoclast-mediated bone resorption, exerting a negative effect on bone mass accumulation in a developing skeleton as well as on the maintaining it in a mature adult skeleton. Thus, antibiotic therapy may cause unforeseen pathophysiological effects that impede the achievement and maintenance of peak bone mass. “Long-term use of antibiotics leads to the decrease in bone density and an increase in its fragility. Measures are needed to mitigate this damage”, the authors of the study “Antibiotic Perturbation of Gut Microbiota Dysregulates Osteoimmune Cross Talk in Postpubertal Skeletal Development” say [1].

However, the antibiotic damage to the musculoskeletal system is not limited to bone tissue. The negative effects of antimicrobials are also felt on the joints. Doctor of Medicine Daniel Horton, University of Pennsylvania, reported in 2014 on the results of the study organized by him with a group of colleagues, which proved that the use of antibiotics increases the risk of juvenile arthritis. Moreover, the more courses of antibiotics a child receives, the higher the risk of developing an inflammatory joint disease [2]. This is another reason why antibiotics should be used in children only as a last resort. If prescribing antimicrobials is unavoidable, the course of antibiotics must be combined with the use of agents for restoring metabolic processes in bones and cartilage.

Unfortunately, references to the lack of effective osteoprotectors for strengthening the musculoskeletal system and preventing fractures are increasingly found in modern scientific literature. The existing agents do not achieve the desired results and have a wide range of adverse effects. They violate bone metabolism and disrupt the natural processes of bone remodeling.

So, starting from the 90s of the last century to the present day, the first choice drugs to strengthen bones and prevent fractures are antiresorbents of the group of bisphosphonates – synthetic pyrophosphate analogue. Their effect is based on the inhibition of osteoclast activity and, due to this, an increase in bone mineral density. However, some large scale independent studies have found that these drugs cannot prevent new fractures, and taking them increases the risk of fractures in the long run [3]. The adverse effects caused by bisphosphonate therapy does not allow recommending them to certain categories of patients, in particular, children, pregnant and lactating women. Bisphosphonates are also contraindicated in persons with chronic kidney disease, disorders of the cardiovascular system, pathologies and severe erosive lesions of the gastrointestinal tract, hypocalcemia, as well as bed patients [4–7].

A group of osteoprotectors such as calcium-containing agents in combination with vitamin D is also widely used. They are recommended to be taken both in combination with bisphosphonates, and in monotherapy. In the first case, the prescription of calcium-containing agents is explained by the fact that bisphosphonates disrupt the conversion of calcium hydroxyapatite to soluble phosphates, i.e. bone demineralization, and in higher doses may disrupt the mineralization process – the binding of soluble calcium to the bone matrix. In the second case, calcium supplements are used to prevent fractures in patients of different age groups with a mineral deficiency in the body [8].

However, recent studies have shown that mineral supplementation cannot reduce the risk of fractures, as well. And their uncontrolled use may cause excessive mineralization of various tissues and organs up to calcinosis, the formation of stones in the kidneys and gall bladder, disorders of the cardiovascular system and the gastrointestinal tract, and occurrence of a malignant tumor [9–16].

In connection with the above, currently there is an acute need for osteobiotics to neutralize the negative impact of various medicaments on the musculoskeletal system and safely restore bone strength in patients of different age.

The term “biotics” was first suggested by Professor A.I.Venchikov in 1942, when explaining the principle of treatment based on natural (physiological) agents that are part of the biotic structures and systems of the body. Those agents not only take part in physiological processes, but also normalize them, increase the body’s resistance to harmful factors and often act as catalysts of a biological nature. Due to a milder therapeutic effect, the agents of this group correct the state of the body not by replacement therapy, but by stimulating the body’s own recovery mechanisms [17].

Thus, osteobiotics are medicaments based on components that are essential for the health of bone and cartilage. They support a healthy calcium metabolism and promote the natural restoration of these tissues.

The first representative of the osteobiotics of this class in Russia is “Osteo-Vit D₃”, developed by “Parapharm” Company. The active ingredients of “Osteo-Vit D₃” are: HDBA organic complex (specially processed drone larvae), vitamins D₃ and B₆. Their synergistic effect provides the restoration of disrupted calcium metabolism in the body and retention of this macroelement in bone tissue. The inclusion of each component in the composition of the osteobiotic is due to the following aspects.

A number of studies have shown the beneficial effect of endogenous androgens on BMD in women of postmenopausal age, who are at the highest risk for fractures [18–21]. But androgen replacement hormonal therapy is associated with an increased risk of cancer, cardiovascular disorders, skin inflammatory reactions and other pathologies. Furthermore, the use of exogenous testosterone causes decrease in the body’s own testosterone production. Drone jelly contained in “Osteo-Vit D₃” is characterized by a high content of gonad type hormonal precursors, originated from the testes, already developed in drone larvae. Because of this, the beekeeping product has a pronounced gonadotropic effect on the human body, safely stimulating the synthesis of endogenous testosterone [22] and thereby increasing BMD.

Vitamin D₃ was included in the composition of the osteobiotic in order to use the body’s own calcium reserves to increase BMD, to redirect the macroelement from vessels and soft tissues to bone tissue [23]. Cholecalciferol is known to improve calcium and phosphorus absorption [24]. Without vitamin D, only 10-15% of calcium and about 60% of phosphorus can be absorbed, but with a sufficient concentration of cholecalciferol calcium absorption increases to 30-40%, and phosphorus – to 80% [25-28]. The effect of vitamin D is largely dependent on the saturation of the body with calcium. When the macroelement is deficient, cholecalciferol will stimulate the absorption of calcium [29], when calcium is excessive – it will contribute to the deposition of calcium salts in soft tissues. Calcium is absent in “Osteo-Vit D₃”, which allows avoiding an overdose of the macroelement and makes the body use its calcium deposits in soft tissues and vessels as a building material for the skeletal system. The protective effect of cholecalciferol metabolites on cartilage tissue of the joints, as well a stheir ability to prevent traumatic osteoarthritis, has been proven [30]. Another beneficial feature of vitamin D as part of this osteobiotic is its ability to exert an immunosuppressive effect and prevent excessive inflammation [31]. Cholecalciferol blocks cytokine-mediated communication of immune cells, and it is precisely the excessive inflammatory reaction that underlies bone metabolism disorders during antibiotic treatment.

Third component of the biological complex “Osteo-Vit D₃” – pyridoxine (vitamin B₆) – is an important nutrient for the connective tissue matrix [32] that the human body cannot synthetize on its own. Along with calcium and vitamin D, pyridoxine, too, has a great effect on the state of bone tissue [33]. This vitamin takes part in the metabolism of a sulfur-containing amino acid – homocysteine, helps to reduce its level in blood plasma. High levels of homocysteine are associated with increased bone fragility and fracture incidence, including hip fractures in elderly people. Animal studies have shown that the deficiency of vitamin B6 can lead to increased levels of homocysteine, resulting in increased free radical production, and so to an oxidative stress. The latter, in turn, can cause endothelial dysfunction, impaired blood supply and nutrition of bone tissue, and osteoporosis. In a seven years study involving 5 thousand people, a correlation was made between high consumption of pyridoxine and a reduced risk of fractures [34]. Patients with low levels of vitamin B₆ in the blood plasma (below 20 nmol/l) showed changes in the structure of cancellous bones [35] as well as a higher average annual bone loss than in people with normal levels of pyridoxine [36].

The combined effect of HDBA organic complex and vitamins D and B6 as parts of “Osteo-Vit D₃” allows the body to safely activate its own restorative mechanisms of bone tissue.

“Osteo-Vit D₃” does not contain calcium, since it has long been proven that fractures do not occur due to the deficiency of this macroelement in the body, but because of calcium metabolism disorders. Thus, “American Journal of Health” (1997) published the results of a 12-years prospective study involving 77,761 women. It turned out that those who consumed large amounts of calcium had fractures more often than those who did not abuse dairy products [37]. This conclusion was later confirmed in a study involving 331,234 men [38].

The effectiveness and safety of the osteobiotic was proven in a number of clinical studies involving children and adults. So, from 2007 to 2013, a study was conducted at N.F.Filatov Penza Regional Children’s Clinical Hospital to explore the therapeutic potential of “Osteo-Vit D₃” in the treatment and prevention of recurrent fractures in children and adolescents with low BMD [39]. 37 participants on the age of 10-18 years with fractures of the long tubular bones of distal upper (28 cases) and lower extremities (9 cases), the presence of cavity formations in the trabecular sections of bones and diagnosed primary osteoporosis were divided into three groups depending on the causes of recurrent fractures. Group 1 consisted of 11 children with vitamin D deficiency, group 2 – 7 children with bone cavities in bone trabecular sections, group 3 – 19 children with low BMD. Patients of the groups 1 and 2 took 1 tablet of “Osteo-Vit D₃” 2 times a day for 3 months three times a year with month-long intervals. Group 3, depending on the method of treatment, was divided into two sub-groups comparable in age and severity of the disease. Sub-group A (10 patients) took “Osteo-Vit D₃” in the same dosage and regimen as patients of the groups 1 and 2. Sub-group B (9 patients) took “Calcium D₃ Nycomed” in a dosage comparable in vitamin D content, containing a commensurable amount of vitamin D and 0.5 g of calcium carbonate. All children underwent bone odensitometry before treatment and 9-11 months after its start.

The therapy with “Osteo-Vit D₃” in the group of children with vitamin D deficiency contributed to the increase of 25(OH)D level to normal after 6 months of treatment. After 1–2 months of treatment, positive dynamics of the main clinical, instrumental and biochemical parameters, a three-fold decrease in the frequency and severity of pain syndrome incidence were noted.

The group of patients with cavities in the trabecular sections of bones showed positive dynamics in 2/3 of the cases: increased BMD, closure of the cavities or their reduction in size, as well as disappearance or reduction of pains (Figures 1, 2).

           а                                          б

Рис. 1. Пациент 15 лет. Полость до начала лечения (а). После лечения почти закрылась (б). Лечение продолжается

Fig. 1. A 15-year-old patient. The cavity before treatment (a). It is almost closed after treatment (b). Treatment is being continued

 

            а                                                 б

Рис. 2. Пациент А. Полости до начала лечения (а). После лечения полости закрылись (б)

Fig. 2. Patient A. The cavity before treatment (a). It is closed after treatment (b)

 

Positive result was not achieved in children with pronounced hormonal imbalance, and namely deficiency of sex hormones, disorders of the thyroid or parathyroid glands. An analysis of the results of therapy in the group 3 showed that the effects of the domestic osteobiotic on increasing BMD and closing cavity formations are not only not inferior to a foreign counterpart, but even superior to it. The consolidation of the bones in the sub-group “Osteo-Vit D₃” also occurred 7-9 days earlier.

In follow-up of children, who received 3 courses of treatment with this osteobiotic, there was not a single case of a recurrent fracture, since the osteobiotic reduces the incidence of falls by improving bone mineralization, strengthening muscles and ligaments.

The use of “Osteo-Vit D₃” was effective in athletes. The supplement prevented functional or organic lesions of musculoskeletal system. Very often, highly qualified athletes of adolescence have hypercalcemic conditions that contributes to the incidence of tear fractures and rupture of ligaments. This is due to the fact that the athlete’s body is forced to build up calcium, necessary for the transmission of electrical signals from the brain to muscles. In this case, the intake of “Osteo-Vit D₃” contributes to the normalization of calcium metabolism and reduction of increased bone mineral density, and prevents recurrent fractures [40].

In addition to the beneficial effects of this domestic osteobiotic on bone tissue, there are convincing data on the effectiveness of “Osteo-Vit D₃” in the treatment of articular pathologies, too. For three years, the Laboratory of Sports Physiology of the Center for Sports Medicine “BAROCOM”, Penza State Institute for Postgraduate Medical Training and Penza State University studied the effectiveness of “Osteo-Vit D₃” in combination with hyperbaric oxygenation in the therapy of gonarthrosis [41].

53 patients aged 45-65 years with osteoarthrosis of the knee were divided into 3 groups, which used the basic treatment complex, which included non-steroidal anti-inflammatory drugs, chondroprotectors and physiotherapeutic procedures. Furthermore, patients of the groups 2 and 3 additionally underwent course exposure to hyperbaric oxygen. The patients of the group 3 took the supplement “Osteo-Vit D₃” 2 tablets 3 times a day during 1 month. The reduction of pain severity for one week of treatment was: in the group 1 – 46.3%, in the group 2 – 60.0%, in the group 3 – 69.6%; in two weeks: in the group 1 – 62.6%, in the group 2 – 70.7%, in the group 3 – 83.9%. The pain severity indicators in the group 3 were reliably lower than similar values in the groups 2 and 1. In addition, in patients of the group 3, the joint flexion decrease angle reliably decreased after two weeks of the treatment from 61.2±0.8 to 43.3±0.7 (p<0.05). This is the best result among three groups. It should be noted that the osteobiotic was well tolerated by patients, no side effects were observed.

The effectiveness and safety of the osteobiotic “Osteo-Vit D₃” in the prevention and treatment of fractures and other disorders of the musculoskeletal system allow it to be recommended for protecting bones and joint tissue from the negative effects of drug therapy, including antibiotic therapy.

However, the protective capabilities of “Osteo-Vit D₃” during antibiotic therapy are not limited only to the skeleton. The protective effect of this osteobiotic covers also the immune and hematopoietic systems.

The intake of antimicrobial medicaments is proven to have a negative effect on the immune system: the proliferation of T and B-cells decreases, the phagocytic ability of mononuclear cells and polymorphic nuclear cells is inhibited. Vitamin D as part of “Osteo-Vit D₃” affects the mechanisms of both innate and acquired immunity, supporting the normal functioning of the immune system, while the active metabolite of vitamin D, cholecalciferol, directly modulates the proliferation of T-lymphocytes, slows down the differentiation of B-cells precursors into plasma cells [42, 43]. Furthermore, cholecalciferol is involved in the production of more than 200 antimicrobial peptides, the most important of which are cathelicidin and β-defensins, endogenous broad-spectrum antibiotics to which addiction does not form in pathogenic microorganisms [43, 44]. HDBA organic complex (drone brood) has adaptogenic properties, its effect on the immune system is comparable to the effect of propolis and exceeds that of the well-known “Apilac” and “Liv.52” [45]. This bee-keeping product contains 28 amino acids, including 9 essential amino acids. Recently, there is increasing evidence that the addition of these organic compounds to the common diet for infectious diseases enhances the immune status. The normal functioning of antibody-mediated (humoral) and cell-mediated immune responses is impossible without vitamin B₆.

HDBA organic complex is the supplier of build-up material for new blood cells as well as the source of nutrients since it contains a complete set of amino acids as well as vitamins and minerals. Evidence of the importance of this is the fact that all 20 proteinogenic amino acids are found in lymphocytes, and in blood lymphocytes – in higher concentrations than in lymphocytes of other organs. Vitamin B6, which is a coenzyme of redox processes, plays a key role in the processes of hematopoiesis and acts as a coenzyme in the synthesis of heme – a non-protein iron-containing part of hemoglobin. Pyridoxine is able to bind to a hemoglobin molecule and affect its ability to capture and release oxygen [46].

The beneficial effect of “Osteo-Vit D₃” on the immune system is especially relevant for athletes. It is known that intense physical activity during exercise have a direct effect on immunocompetent cells. This is manifested in a sharp drop in all immunity parameters, depletion of the physiological reserves of the immune system, and the development of secondary immunodeficiency. In this case, the osteobiotic can have three benefits: it helps strengthen bone tissue, normalizes the immune system, and forms a protective barrier against infections.

 

Conclusion

Osteobiotics are combinations of biologically active components that are extremely important for the health of bone and cartilage tissues. They maintain a healthy calcium metabolism and contribute to the natural restoration of tissues. The active ingredients of the osteobiotic “Osteo-Vit D₃” are HDBA organic complex (drone homogenate), contributing to the restoration of hormonal balance and the production of collagen, vitamin D₃, which helps the body to use its own calcium reserves to increase bone mineral density, as well as vitamin B₆, which helps to reduce plasma homocysteine levels. The synergistic effect of the said substances provides the restoration of impaired calcium metabolism in the body as a whole and in bone tissues in particular.