Forosa, 4 pcs., 70 mg, film-coated tablets

Instructions for use FOROSA

Forosis can cause local irritation of the mucous membrane of the upper gastrointestinal tract. Because there is a risk of worsening concomitant diseases, caution should be exercised when prescribing Forosa to patients with upper gastrointestinal diseases such as dysphagia, esophageal disease, gastritis, duodenitis or ulcers, as well as to patients who have recently (within the last year) had a serious gastrointestinal disease ( for example, gastric ulcer, acute gastrointestinal bleeding) or surgery of the upper gastrointestinal tract, excluding pyloroplasty. In patients with Barrett's esophagus, the benefits and risks of treatment with alendronate should be individually assessed.

Esophageal side effects (in some cases severe and requiring hospitalization) such as esophagitis, ulcers or erosions of the esophagus, in rare cases complicated by stricture or perforation of the esophagus, have been described in patients treated with alendronate. Therefore, the physician should be alert for any sign or symptom of a possible esophageal reaction. Patients should be instructed to stop taking Forosa and seek medical attention if symptoms of esophageal irritation develop, such as dysphagia, pain when swallowing, chest pain, or new/worsening heartburn.

The risk of severe esophageal side effects increases in patients who misuse Forosa and/or continue to take the drug after developing symptoms indicating esophageal irritation. It is very important to give detailed instructions when prescribing and explain them to the patient. Patients should be advised that the risk of esophageal injury may increase if they do not follow these instructions.

There are post-marketing reports of rare cases of gastric and duodenal ulcers, some of them with severe course and complications. A causal relationship with the drug cannot be excluded.

Forosa is not recommended for use in patients with impaired renal function and GFR below 35 ml/min.

Before starting treatment with Forosa, hypocalcemia must be corrected. Before you start taking Forosa, it is also necessary to effectively compensate for other disorders of mineral metabolism (for example, vitamin D deficiency and hypoparathyroidism). In such patients, serum calcium levels and symptoms of hypocalcemia should be monitored during treatment with Forosa.

Due to the positive effects of Forosa on bone mineralization, a decrease in serum calcium and phosphorus levels may be observed. It is usually mild and asymptomatic. However, in rare cases, symptomatic hypocalcemia has been described, which is sometimes severe and occurs in patients with predisposing conditions (eg, hypoparathyroidism, vitamin D deficiency and cases of intestinal calcium malabsorption).

Therefore, it is especially important to ensure that a patient taking glucocorticoids gets enough calcium and vitamin D.

Osteonecrosis of the mandible, mainly associated with tooth extraction and/or local infection (including osteomyelitis), has been described in patients with cancer receiving IV bisphosphonates along with other treatment regimens. Many of these patients also received chemotherapy and corticosteroids. Osteonecrosis of the mandible has also been described in patients taking oral bisphosphonates.

In patients with underlying risk factors (eg, cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene, periodontitis), dental examination and appropriate prophylactic treatment should be performed prior to initiating bisphosphonate treatment.

These patients should avoid invasive dental procedures if possible during treatment. In patients with osteonecrosis of the mandible that develops during bisphosphonate treatment, surgery may aggravate the disease. There are no data suggesting a reduction in the risk of osteonecrosis of the mandible after discontinuation of bisphosphonate treatment in patients requiring dental procedures.

When developing a patient management plan, the physician must individually assess the benefits and risks of treatment.

Bone, joint and/or muscle pain has been reported in patients taking bisphosphonates. These symptoms were rare and/or rarely disabling. The time for symptoms to develop varied from one day to several months after the start of treatment. Most patients experienced improvement in symptoms after stopping treatment. Some have experienced a return of symptoms when they take the same drug or a different bisphosphonate again.

Stress fractures (also known as osteoporotic fractures) in the proximal femoral shaft have been reported with long-term use of alendronic acid (time to fracture ranged from 18 months to 10 years in most cases). These fractures occurred with minimal trauma or spontaneously. Some patients have complained of hip pain, often accompanied by radiographic evidence of a stress fracture, several weeks or months before a complete femur fracture. Such fractures were often bilateral, so when the femoral shaft is fractured during treatment with bisphosphonates, it is important to examine the contralateral limb. These fractures are characterized by poor healing. In such cases, discontinuation of bisphosphonates is recommended, depending on an individual assessment of the benefits and risks of such a decision.

If you miss a dose, take the pill the next morning after you remember to do so. You should not take two tablets on the same day. You must return to taking the pill on the originally chosen day of the week.

Forosa does not affect the ability to drive vehicles or operate machinery.

Forosa, 4 pcs., 70 mg, film-coated tablets

Take Forosa® tablets only with plain water, because other drinks (including mineral water, tea, coffee, fruit juices) impair the absorption of the drug. Taking alendronate before bed or in a horizontal position increases the risk of developing esophagitis.

If symptoms of esophageal irritation occur, such as dysphagia, chest pain, or new/worsening of existing heartburn, patients should consult a physician to evaluate the possibility of continuing therapy. The risk of severe esophageal side effects is greater in patients who take alendronic acid not in accordance with these instructions and/or who continue to take it after symptoms suggestive of esophageal irritation have occurred. It is important to explain in detail to the patient the rules for taking the drug and make sure that he understands them. Patients should be aware of the increased risk of adverse events from the esophagus if they deviate from the instructions.

Before starting therapy with Forosa®, correction of hypocalcemia and other metabolic disorders (such as vitamin D deficiency) is necessary. Due to the increase in bone mineral density during alendronate therapy, a slight clinically asymptomatic decrease in serum calcium and phosphate levels is possible, especially in patients receiving corticosteroids, in whom calcium absorption may be reduced. Therefore, ensuring that sufficient amounts of calcium and vitamin D enter the body is especially important in patients receiving corticosteroids.

Patients should be warned that if they accidentally miss a dose of the drug once a week, they should take 1 tablet. in the morning of the next day (it is unacceptable to take 2 tablets in one day). Subsequently, you should continue to take 1 tablet. on the day of the week that was chosen at the beginning of therapy.

There is also evidence of osteonecrosis of the jaw in patients with osteoporosis receiving oral bisphosphonates. Before prescribing bisphosphonate therapy, patients with associated risk factors (eg, cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene, anemia, coagulopathy, infection, gum disease) should undergo a dental examination with appropriate preventive dental treatment. During treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw during bisphosphonate treatment, dental surgery may worsen the condition.

There are no data regarding the possible reduction in the risk of osteonecrosis of the jaw after discontinuation of bisphosphonates in patients requiring dental intervention.

Low-energy fractures (also known as stress fractures) of the proximal femoral shaft may occur in patients taking alendronic acid long-term. Fractures can occur after minimal or no trauma, and some patients may experience hip pain, often with outward signs of stress fractures weeks/months before a complete femur fracture occurs.

Low-energy proximal femoral shaft fractures were often bilateral, so patients with a long-standing femoral shaft fracture taking bisphosphonates should have the contralateral hip evaluated. It is advisable to discontinue bisphosphonates in patients with stress fractures after assessing their condition based on an individual assessment of the risk/benefit ratio.

The decision to proceed with treatment must be made individually for each patient after a careful risk/benefit assessment, especially for patients with Barrett's esophagus.

Impact on the ability to drive vehicles and engage in other activities that require increased concentration and speed of psychomotor reactions.

Alendronic acid does not affect the ability to drive vehicles and engage in other activities that require increased concentration and speed of psychomotor reactions.

Special precautions when disposing of unused drug.

There is no need for special precautions when disposing of unused drug.

Relevance of the problem

The social significance of any disease is determined by its prevalence, difficulties of diagnosis and therapy, and significant impact on disability and mortality rates.
According to these criteria, diseases caused or accompanied by disorders of phosphorus-calcium metabolism absolutely correspond to the status of socially significant ones. In the practice of an endocrinologist, diseases accompanied by impaired calcium metabolism occupy a significant place. Severe disturbances of mineral metabolism are observed in diabetes mellitus, pathology of the thyroid gland and adrenal glands, hyper- and hypoparathyroidism, peri- and postmenopause, and age-related androgen deficiency. Clinical manifestations of calcium and phosphorus metabolism disorders are quite varied, but the most well known manifestations are those associated with damage to bone tissue, including osteoporosis. As a cause of disability and mortality in patients from bone fractures, osteoporosis ranks fourth among non-communicable diseases [1]. According to statistics, only 25% of patients are completely cured after a hip fracture, 50% of patients remain disabled, and in 25% of cases, a fracture due to osteoporosis leads to the death of patients. In Russia, osteoporosis has been detected in 10% of the population (more than 14 million people) [3, 4]. Every year, 3 million vertebral fractures are recorded, more than 150 thousand of the radius and more than 40 thousand of the proximal femur.

In the medical literature, osteoporosis is sometimes figuratively called a “silent epidemic.” The disease is asymptomatic for a long time and is first diagnosed after a fracture occurs. The term “osteoporosis” as the name of a pathological process is usually used when talking about primary osteoporosis (Fig. 1). The pathology of the endocrine system is usually associated with manifestations of secondary osteoporosis, which is observed in patients against the background of increased secretion of parathyroid hormone (PTH), caused by secondary causes, incl. endocrine diseases (Fig. 2). From the group of diseases designated as primary osteoporosis, the scope of activity of endocrinologists includes osteoporosis caused by postmenopause, and, in our opinion, osteoporosis caused by androgen deficiency can be rightfully included.

The state of phosphorus-calcium metabolism in normal and pathological conditions

The level of calcium in the human body is one of the most significant constants. Reliable proof of this is the minimal spread of the values ​​of the given indicators. Laboratory criteria for the normal level of total calcium in the blood serum are 2.1–2.6 mmol/l; ionized – 1.1–1.3; protein-bound – 0.9–1.1; complexed – 1.18 mmol/l. In the blood, calcium is presented in three forms. About 40% of it is in the form of protein-bound compounds, almost half is free (including ionized) calcium, 10% is complexes with citrates and phosphates.

As a rule, extracellular calcium regulates muscle contractile activity, synaptic signal transmission in nervous tissue, platelet and erythrocyte aggregation, the coagulation process, and the secretion of hormones and biologically active compounds. Intracellular calcium regulates the processes of the cell cycle and growth, the permeability of cell membranes, the strength of muscle contractions, as well as the secretion of hormones and biologically active factors.

Calcium is an important component in regulating the functioning of the cardiovascular system (contractile function, maintaining normal rhythm and conduction, blood pressure control), and has antioxidant, anti-inflammatory, anti-edematous and anti-atherosclerotic effects.

The metabolism of calcium and phosphorus in a healthy body is in dynamic equilibrium; compensatory mechanisms regulate it in hyper- or hypocalcemic conditions.

The implementation of this control is ensured by adequate levels of PTH, calcitonin, vitamin D and other hormones:

• PTH: regulates bone resorption indirectly through osteoclasts;
• calcitonin: inhibits bone resorption by acting directly on osteoclasts;
• insulin: stimulates matrix synthesis and cartilage formation, normalizes mineralization;
• somatotropic hormone: maintains overall bone mass by regulating the synthesis of insulin-like growth factor type 1 (IGF-1), stimulates the synthesis of 1,25-dihydroxy vitamin D;
• vitamin D is responsible for bone mineralization, stimulates the synthesis of osteocalcin by osteoblasts and increases the concentration of IGF-binding proteins;
• glucocorticoids: stimulate bone resorption, reducing calcium absorption in the intestine (decreased PTH secretion);
• Thyroid hormones: stimulate bone resorption;
• estrogens: suppressing the production of interleukins (IL-1, -6), reduce bone resorption, maintain bone mass by regulating the activity of the TGF-β gene;
• androgens: have an anabolic effect on bone tissue.

The vital activity of the skeletal system is based on two interrelated processes: the creation (formation) of new bone and the process of destruction (resorption) of old bone. These processes in the skeletal system occur at different rates throughout a person’s life. From 1–2 to 10% of bone mass is exchanged annually. The latter reaches its maximum value by the age of 16–20 years, therefore childhood and adolescence are critical periods for the formation of a strong, healthy skeleton. Upon reaching the peak, a balance between the processes of synthesis and resorption occurs, which continues until 40–45 years in women and 50 years in men. Then bone loss begins, which is more significant in women after menopause [3, 4].

Factors that influence bone formation and strength include:

• genetic;
• growth factor;
• nutritional factors;
• physical activity;
• environmental factors.

The bone of a healthy person is living, active tissue. It is strong, able to withstand significant loads without breaking, but at the same time flexible, able to absorb energy, deform and not break. Such contradictory properties of bone are achieved due to the special composition and structure (weaving type 1 collagen into a triple helix). With disturbances in phosphorus-calcium metabolism, the situation changes. The effect of loading on a bone with insufficient mineralization causes the bone to bend excessively and fracture, however, if loading occurs on a bone with excessive mineralization, it will underflex and also fracture.

Hypercalcemia, accompanied by excessive production of PTH, is observed in primary, secondary hyperparathyroidism, multiple endocrine neoplasia, pseudohyperparathyroidism (ectopic production of PTH) and familial isolated hyperparathyroidism. Hypercalcemia syndrome can develop against the background of other endocrinopathies - thyrotoxicosis, hypothyroidism, eosinophilic pituitary adenoma (acromegaly), hypercortisolism, pheochromocytoma, VIPomas. In addition to endocrine diseases, the causes of hypercalcemia and objects for differential diagnosis are an overdose of vitamin D, malignant tumors, acute and chronic renal failure, immobilization after bone fractures, and certain medications. Excessive calcium intake (more than 2 g/day) can also lead to the development of hyperparathyroidism.

Hypocalcemia is a condition associated with primary or secondary deficiency of PTH production, vitamin D deficiency and resistance to PTH (pseudohypoparathyroidism). The main reasons: autoimmune process in the parathyroid glands, postoperative or radioiodine hypoparathyroidism, diabetes mellitus.

Dysfunction of the parathyroid glands can manifest itself as a component of various genetic syndromes (DiGeorge syndrome, Wilson's disease, hemochromatosis, etc.) and autoimmune polyglandular syndrome type I (hypoparathyroidism, chronic generalized granulomatous candidiasis and chronic adrenal insufficiency). Calcium deficiency is accompanied by endocrine disorders associated with age-related changes in the reproductive system - androgen deficiency in men and postmenopausal processes in women.

In addition to endocrine disorders, calcium deficiency may be accompanied by diseases of the gastrointestinal tract, kidneys, hypovitaminosis D, increased levels of magnesium in the blood serum, and the use of medications (hormonal, laxatives, antacids, diuretics, adsorbents, anticonvulsants, tetracycline).

Factors that contribute to calcium deficiency in the body include a sedentary lifestyle, consumption of a lot of proteins, sugar, salt, animal fats, acidic foods (spinach, rhubarb, etc.) [5].

An imbalance of phosphorus-calcium metabolism contributes to the progression of atherosclerosis, the development of arthrosis and dorsopathy, arterial hypertension, but the main manifestation remains osteoporosis, leading to a significant increase in the risk of bone fractures [6, 7].

Primary hyperparathyroidism

The most common cause of hypercalcemia and hypophosphatemia. The disease has been repeatedly presented since 1981 in the scientific medical literature under various names: Recklinghausen's disease, Burnett's syndrome, fibrous osteodystrophy, primary hyperparathyroidism. The prevalence of the disease is 0.05–0.10% of the population and is observed approximately 4 times more often in women than in men.

In 80–89% of cases, the cause of the disease is a solitary adenoma of the parathyroid gland; multiple adenoma (2–3%), hyperplasia of the parathyroid glands (2–6%) and cancer (0.5–3.0%) are much less common.

Primary hyperparathyroidism is observed in 90% of patients with multiple endocrine neoplasia type I (MEN I) and in 50% of patients with MEN type IIa. Excessive production of PTH and lack of suppression of secretion in response to hypercalcemia lead to accelerated bone resorption and leaching of calcium from bones, reducing the threshold for phosphorus reabsorption. Glomerular filtration of calcium and urinary excretion of phosphorus increases. Hypercalcemia is maintained by increased tubular reabsorption of calcium and increased intestinal calcium absorption. The symptoms of the disease are quite varied. Patients complain of general weakness, loss of appetite, nausea, vomiting, constipation, weight loss, bone pain, arthralgia, bone deformation, muscle weakness, convulsions, polyuria, polydipsia, memory impairment, depression, calcifications of soft tissues and cornea, swelling of the face, dysfunction of the cardiovascular system. The predominance of certain symptoms makes it possible to conditionally classify the manifestations of the pathology of a particular patient as bone, visceral or renal forms of hyperparathyroidism. The least difficult form to diagnose is the “bone” form, in which variants of damage such as systemic osteoporosis, osteitis fibrosa or Paget’s disease are possible. X-ray examination allows us to record typical bone changes in the form of osteoporosis, pathological fractures, subperiosteal bone resorption, cystic formations in the area of ​​the epiphyses, and skeletal deformities. Hyperparathyroidism is quite common, but, unfortunately, diagnosing this disease is quite difficult.

Secondary hyperparathyroidism

A condition associated with increased PTH production in response to prolonged hypocalcemia. In patients with thyrotoxicosis, increased catabolic processes lead to increased bone tissue resorption, because Thyroid hormones activate predominantly osteoclasts. The predominance of bone resorption over its formation can lead to hypercalcemia and calciuria, and with long-term uncompensated hyperthyroidism, the development of osteopenia can be considered an expected complication, especially in young patients.

The occurrence of osteoporosis against the background of hypothyroidism is possible, but this is associated with hormonal replacement therapy (overdose of thyroid drugs). For patients with hypercortisolism, both primary and iatrogenic, excess production of glucocorticoids is accompanied by suppression of osteoblast activity and inhibition of calcium absorption in the intestine. Hypocalcemia leads to increased production of PTH, development of secondary hyperparathyroidism and activation of osteoclasts.

A decrease in insulin secretion in patients with type I diabetes mellitus is accompanied by a decrease in the activity of osteoblasts and suppression of the secretion of 1,25(OH)2D3 in the kidneys. Bone loss is also influenced by increased glucocorticoid secretion in response to hypoglycemia and decreased physical activity.

Primary hypoparathyroidism

Insufficiency of PTH secretion by the parathyroid glands, decreased calcium resorption in the renal tubules, decreased calcium absorption in the intestine, leading to hypocalcemia. The main causes are surgical interventions on the thyroid and parathyroid glands, treatment with radioactive iodine, developmental disorders of the parathyroid glands (congenital hypoplasia, DiGeorge syndrome, etc.), autoimmune processes and idiopathic hypoparathyroidism. The disease can occur in acute and chronic forms. The leading syndromes include tetany and autonomic dysfunction. Confirmation of the diagnosis involves conducting provocative tests: Trousseau, Chvostek, Schlesinger, Weiss.

Postmenopausal osteoporosis

Postmenopausal osteoporosis occurs most often in clinical practice and is characterized by rapid development. Postmenopausal women experience a 15–20% decrease in bone mass over 5–10 years. The main reason is estrogen deficiency, which leads to an increase in the number and activity of osteoclasts. Increased resorption leads to irreversible bone loss. High activity of osteoclasts promotes perforation of trabeculae at the site of resorption, and the microarchitecture of the bone is disrupted. The trabecular bone is primarily affected, so the localization of early osteoporetic fractures is the carpal bones and vertebrae.

Multiple endocrine neoplasia

This name combines a group of syndromes caused by tumors (rarely hyperplasia) of several endocrine glands simultaneously. Most tumors are of neuroectodermal origin and have a malignant course. In the middle of the 20th century. P. Wermer described a syndrome that included a combination of a tumor of the parathyroid glands, pituitary glands and pancreas, and called it multiple endocrine adenomatosis (now MEN I). A little later, JH Sipple described the syndrome of combined symptoms of thyroid cancer and pheochromocytoma (MEN IIa). Among 50% of these patients, parathyroid adenoma and hyperparathyroidism are observed. Difficulties in diagnosis are due to the fact that symptoms of damage to different endocrine organs do not appear simultaneously. Sometimes the disease begins with hyperparathyroidism with characteristic clinical symptoms, and symptoms of damage to other endocrine glands manifest much later, so it takes much more time to establish a final diagnosis.

Problems of diagnosing disorders of phosphorus-calcium metabolism

The problem of diagnosing disorders of phosphorus-calcium metabolism is associated with the characteristics of the disease. The absence of pronounced clinical manifestations in the initial stages of the disease leads to the fact that a visit to an endocrinologist is far from the first position in the diagnostic chain. Therefore, the diagnosis of disorders of phosphorus-calcium metabolism of an endocrine nature is made quite late. As a rule, the first signal to begin examining a patient is the occurrence of a pathological fracture. Densitometry does not always immediately provide an unambiguous answer. Among women aged 50 years and over, 50% have fractures but do not have osteoporosis, as measured by bioenergetic X-ray absorbitiometry (Wainwright SA et al., 2005). In a population of women aged 50 years and older, 96% of typical fractures can occur without a decrease in bone mineral density (BMD) (Kanis JA et al., 2001).

Still, some symptoms of osteoporosis are present. These include pain in the back and lower back, forward curvature of the spine, a decrease in height by several centimeters over the course of a year, leg cramps, brittle nails, and the appearance of early gray hair. Typically, the appearance of these symptoms leads patients not to an endocrinologist, but to a neurologist and therapist. Osteoporosis should be suspected if height has decreased by more than 2 cm in one year or by 4 cm over several years.

The traditional approach to diagnosing osteoporosis is based on assessing the risk of fracture. Risk factors for osteoporosis and fractures are usually divided into major and minor.

Big risk factors:

• age over 65 years;
• history of previous fractures (during daily physical activity in persons over 40 years of age);
• vertebral compression fractures;
• family history of osteoporetic fractures;
• long-term use of glucocorticoids (more than 3 months);
• female;
• low BMD;
• estrogen deficiency: early menopause (up to 40–45 years), surgical menopause (up to 40–45 years);
• primary hyperparathyroidism;
• predisposition to falls (muscle weakness, decreased visual acuity, decreased proprioceptive sensitivity, use of benzodiazepines);
• malabsorption syndrome;
• long-term immobilization;
• osteopenia;
• hypogonadism.

Minor risk factors:

• rheumatoid arthritis, diabetes mellitus;
• history of clinical hyperparathyroidism;
• continuous anticonvulsant therapy;
• insufficient calcium intake;
• vitamin D deficiency;
• long-term immobilization;
• smoking (decreased estrogen production);
• alcohol abuse (inhibits osteoblasts, suppresses bone resorption, disrupts vitamin D metabolism, increases age-related androgen deficiency);
• body mass index <20 kg/m2, weight <57 kg;
• weight loss of more than 10% at age 25;
• caffeine abuse;
• long-term heparin therapy.

Osteoporotic (minimal trauma fracture) is defined as a fracture that occurs spontaneously or from a fall from a height no higher than one's own height, including fractures caused by activities such as coughing, sneezing, or sudden movement (for example, opening a window). And also in a situation where a patient’s x-ray reveals a vertebral compression fracture, regardless of whether symptoms of compression are detected or not.

Laboratory diagnostics involves determining blood levels of calcium, phosphorus, other microelements, biochemical markers of bone formation (alkaline phosphatase, osteocalcin, PINP N (terminal propeptide of type 1 procollagen) and markers of bone resorption. Markers of bone resorption (beta-cross laps) indicate on accelerated bone turnover, decreased BMD, and fractures.The combination of a high level of bone resorption markers (for example, the degradation products of type I collagen - N-telopeptide [NTX] in the urine or C-telopeptide in the blood serum) with a low level of BMD on densitometry or previous fractures indicates an increased risk of new fractures. Repeated BMD studies during therapy are usually carried out at intervals of 1–2 years. Treatment is considered effective if no negative dynamics are observed in BMD indicators within a year.

Determination of the level of PTH and osteocalcin is a mandatory component of the examination for any form of osteoporosis. In the diagnosis of disorders of phosphorus-calcium metabolism, histomorphometry uses both methods of X-ray examination, densitometry, and standard radiography.

Any adult patient who has sustained a vertebral, proximal femoral, or radial fracture due to minimal trauma should be considered at high risk for fracture development and a candidate for treatment for osteoporosis (even if BMD values ​​do not meet criteria for a diagnosis of osteoporosis). Women over 70 years of age with a previous fracture are candidates for treatment of osteoporosis without densitometry.

The choice of treatment tactics for various types of phosphorus-calcium metabolism disorders

The main goal of treating patients with diseases accompanied by hypercalcemia, in addition to the etiopathogenetic treatment of the underlying disease, is to reduce the leaching of calcium from the bones or increase the flow of calcium into the bone.

In the treatment of primary hyperparathyroidism, the main and most radical method is adenomectomy of the parathyroid gland. However, not in all cases this operation can be performed quickly or radically. If the patient refuses surgery, if there are absolute or relative contraindications, or if the operation is unsuccessful, drug treatment should be prescribed. Synthetic phosphate binders are used in short courses (2–4 weeks), which eliminates hypercalcemia and prevents the formation of kidney stones.

Positive results from the use of estrogen-gestagen drugs have been obtained from postmenopausal women. A good effect is ensured by the use of active metabolites of vitamin D and bisphosphonates, the importance of which increases in the presence of contraindications to hormone replacement therapy. The use of bisphosphonates in standard doses allows normalization of calcium levels in 80% of patients. Treatment of osteoporosis in patients with age-related androgen deficiency involves prescribing testosterone replacement therapy.

Treatment of secondary hyperparathyroidism is determined by the underlying pathology that caused its formation and the stage of medical care. In the treatment of secondary osteoporosis, calcitriol, calcium supplements and bisphosphonates are used. Parathyroidectomy may also be the treatment of choice for the treatment of secondary hyperparathyroidism. The absolute indications are the occurrence of osteitis fibrosa, failure of conservative therapy, persistent hypercalcemia with an increased PTH value, disseminated skin necrosis, and soft tissue calcifications.

Treatment of hypoparathyroidism involves a diet rich in calcium (mainly milk-vegetable), calcium salts, replacement therapy with PTH and its analogues, as well as the use of vitamin D and combination drugs (vitamin D + calcium supplements, dehydrotachysterol, AT-10, etc. ).

Treatment of osteoporosis due to both primary and secondary causes has common approaches.

Non-drug therapy:

• physical exercise;
• reducing the risk of falls;
• diet;
• to give up smoking;
• food enriched with calcium and vitamin D.

Drug therapy:

• hormone replacement therapy;
• tibolone (synthetic steroid);
• selective estrogen receptor modulators;
• bisphosphonates;
• calcitonin;
• calcium preparations.

Among the non-drug treatments listed, the patient can be responsible for quitting smoking and reducing the risk of falls. As for physical exercises, there should be a mandatory consultation with a specialist and an individual complex of physical therapy developed for each patient.

Whatever the origin of the disease that leads to the development of osteoporosis, diet is an important component of treatment. Under normal conditions of the body, to ensure the basic processes regulated by phosphorus-calcium metabolism, a person should receive 0.5 g of calcium per day. However, many guidelines recommend 1 g of calcium per day, this is due to the fact that only 50% of the consumed dose is absorbed in the intestines due to the low ability of calcium to form soluble compounds. It is for this reason that calcium is better absorbed from foods that have not been subjected to heat treatment. When foods are heated, calcium forms stable compounds and is practically not absorbed by the body. Higher doses of calcium under physiological conditions are required by a growing body, a woman during pregnancy, people during significant physical and mental stress, and in winter. Patients with osteoporosis must consume foods rich in calcium, vitamins (D, A, E), and microelements (magnesium, copper, zinc, selenium).

As people age, the skin's ability to produce D3 and absorb it in the intestines decreases. Older people are less likely to be outdoors in direct sunlight, which, of course, cannot but affect the formation of endogenous vitamin D.

Drug correction of phosphorus-calcium metabolism disorders is not an easy task. A fairly limited group of drugs has been identified that are used as pathogenetic therapy. In the practice of an endocrinologist, bisphosphonates, calcium and vitamin D preparations are successfully used [8, 9].

Criteria for assessing the effectiveness of drugs for the treatment of osteoporosis: reduction in the incidence of fractures during 3-5 years of treatment (main criterion), increase in bone mineral density, normalization or improvement of the profile of markers of bone metabolism, improvement in bone quality (histomorphological studies), improvement in the quality of life of patients (increased physical activity, pain reduction).

Calcium preparations have been used for a long time in the treatment of primary osteoporosis. Tablet forms of calcium supplements are more often used; the main means that promote better absorption of calcium from the gastrointestinal tract are well known:

• protein foods (amino acids improve calcium transport into the cell);
• lemon juice (increases the absorption of calcium salts);
• choleretic agents (bile acids improve calcium utilization in the small intestine);
• sufficient amount of fluid (1.5–2.0 l/day).

Ionized calcium has physiological activity; it activates the plastic function of osteoblasts and osteocytes, participates in the formation of bone tissue, and forms the mineral basis of the skeleton. Calcium preparations compensate for ion deficiency, inhibit the activity of osteoclasts and reduce bone resorption. Calcium salts are effective in the treatment of osteoporosis if they enter the body in an amount of at least 1500 mcg/day (in terms of ionized calcium). The lowest calcium content in 1 g of salt is found in calcium gluconate, the highest in calcium carbonate and calcium phosphate. In addition to monocomponent preparations of calcium salts, two-component preparations are used: calcium salts + vitamin D3.

Vitamin D is used for various disorders of phosphorus-calcium metabolism - in the complex therapy of osteoporosis, hypoparathyroidism, osteomalacia, Fanconi syndrome. The concept of “vitamin D” combines two natural forms – D2 (ergocalciferol) and D3 (colecalciferol), their structural analogues and active metabolites. Native products (colecalciferol, ergocalciferol) and a vitamin D2 analogue (dihydrotachysterol) have moderate activity. Currently, active metabolites are more often used for therapeutic purposes - calcitriol [1α,25-(OH)2D3], alfacalcidol [1α-(OH)D3], calcipotriol. All vitamin D preparations in the body are converted into calcitriol and provide the same pharmacological effect: increased calcium absorption in the intestine (formation of calcium-binding proteins inside enterocytes), inhibition of increased bone resorption, normalization of remodeling processes and leaching of calcium from bones, suppression of PTH secretion, improvement of muscle tissue function . Under the influence of calcitriol and alfacalcidol, there is also an increase in the synthesis of type 1 collagen and matrix proteins (osteocalcin and osteopontin) in osteoblasts, which play an important role in the processes of formation and mineralization of bone tissue. The use of calcitriol helps suppress the activity of 1α-hydroxylase and stimulates the activity of another renal enzyme - 24α-hydroxylase, increases the formation of the active metabolite - 24α,25(OH)2D3, which plays an active role in the healing processes of microfractures and the formation of microcalluses in bones, increases bone tissue density .

Vitamin D preparations have been used for a long time to prevent and treat osteoporosis. Physiological replacement doses of native vitamin D range from 400–800 to 1000–2000 IU/day. In case of metabolic disorders, dosages can be increased from 10 thousand to 25 thousand IU/day. Therapy is carried out over several months or years.

Calcitriol has proven effectiveness in the treatment and prevention of secondary hyperparathyroidism. The use of calcitriol lowers PTH levels and improves bone structure. The dose depends on the severity of the patient’s condition and the route of administration (oral, intravenous).

However, the risk of developing hypercalcemia and hypercalciuria should be taken into account during long-term treatment with high doses of vitamin D. Alfacalcidol is safer with long-term use and can be used in patients with kidney disease.

Bisphosphonates are the “gold” standard in the treatment of osteoporosis, regardless of whether it is primary or secondary [8]. The name of this group of drugs was formed due to the presence in the chemical structure of a carbon atom bonded to two phosphorus atoms (non-hydrolyzable PCP bond). The structure of bisphosphonates is close to endogenous pyrophosphate. First-generation bisphosphonates inhibited the resorptive activity of osteoclasts due to the formation and accumulation of metabolites that disrupt the normal functioning of osteoclasts. The first generation bisphosphonates (etidronate, clodronate and tiludronate) were used primarily to treat Paget's disease (osteitis deformans) and later in the treatment of osteoporosis. Today, etidronate, tiludronate, pamidronate, ibandronate and zoledronate are practically not used in the treatment of osteoporosis; the main indications for their use remain Paget's disease and tumor forms of hyperthyroidism.

The formula of new generation bisphosphonates - aminobisphosphonates - contains a nitrogen atom (alendronate, risendronate), which changes their mechanism of action, and due to the inhibition of farnesyl pyrophosphatase and other stages of mevalonate metabolism, the differentiation of osteoclast precursors is disrupted and osteoclast apoptosis is enhanced. As a result, the level of bone resorption markers decreases, bone mineral density increases and the risk of fractures decreases.

All of the above has expanded the horizons of use of new generation bisphosphonates. Alendronate is effectively used both for juvenile and immobilization osteoporosis, and for osteoporosis caused by endocrine disorders (hyperthyroidism, hypercortisolism, estrogen and androgen deficiency).

The use of bisphosphonates must be accompanied by certain precautions: the drugs must be taken on an empty stomach with plenty of water. The most common side effects are: abdominal pain, dyspeptic disorders (constipation or diarrhea, flatulence), dysphagia, heartburn; muscle pain, bone pain. Bisphosphonates are not metabolized in the body, so they are excreted in the urine almost unchanged.

Bisphosphonates are contraindicated during pregnancy, lactation, severe renal impairment (creatinine clearance less than 30 ml/min), and hypersensitivity. One should also remember about the “rebound phenomenon” - increased bone resorption during treatment with calcium salts after discontinuation of bisphosphonates.

Forosa® is the drug of choice in the treatment of phosphorus-calcium metabolism disorders in patients with endocrine pathology

In the treatment of phosphorus-calcium metabolism disorders in patients with endocrine pathology, the requirements for choosing a drug for their correction are increasing. Not all drugs used in the treatment of primary osteoporosis are sufficiently effective in secondary osteoporosis of endocrine origin. On the other hand, according to the requirements of modern medicine, the effectiveness of any drug must be proven by multicenter randomized studies. In accordance with these criteria, the activity of nitrogen-containing bisphosphonates (alendronate, risendronate) has been confirmed [3], so they are the first-line drugs for the treatment of osteoporosis.

One of the most optimal bisphosphonate formulas that we use today is Forosa® - sodium alendronate trihydrate, a non-hormonal specific inhibitor of osteoclastic bone resorption that suppresses osteoclast activity. Forosa® stimulates osteogenesis, restores a positive balance between bone resorption and restoration, increases bone mineral density (regulates phosphorus-calcium metabolism), promotes the formation of bone tissue with a normal histological structure. The advantages of the drug are associated with the frequency of use (70 mcg once a week), high effectiveness for osteoporosis of any type, both in women and men. And this is a very important aspect in the treatment of secondary osteoporosis against the background of age-related androgen deficiency and the prevention of fractures.

There are no restrictions for its use in elderly patients and patients with impaired liver function or moderate renal impairment (Cl creatinine > 35 ml/min). The drug is of particular value for endocrinological practice due to the proven effectiveness of its use in patients with hypercortisolism, incl. for the treatment of osteoporosis caused by long-term use of corticosteroids. Forosa does not affect concentration or the ability to drive.

Conclusion

The clinical effectiveness of alendronate has been repeatedly proven in randomized studies in patients with osteoporosis (recommendation level A). It is effective not only for primary forms of hypoparathyroidism, but also for disorders of phosphorus-calcium metabolism in patients with hyperparathyroidism, hypercortisolism, thyrotoxicosis, and diabetes mellitus. On average, Forosa reduces the risk of fractures of various locations by 50%, and the risk of multiple vertebral fractures by 90%. Of course, the drug is also endowed with some common disadvantages of all bisphosphonates: low bioavailability of tablet forms, nephrogenic route of elimination, limited use in patients with impaired renal function, side effects in the form of dyspeptic disorders, pain in bones and muscles, allergic reactions, but subject to the recommendations for use The drug Forosa® allows for high efficiency in the correction of phosphorus-calcium metabolism disorders in endocrine diseases.

Treatment of osteoporosis: experience with alendronate

Using advanced, primarily radiological, research methods, the development and implementation of new methods of prevention and treatment, as well as active and purposeful educational activities of the International Osteoporosis Foundation (IOF) and its 186 national societies in 90 countries, including the Russian Association for Osteoporosis osteoporosis, the social and medical significance of the disease has increased significantly. Official registration of the incidence of AP began in the Russian Federation in 1999, and over the past 10 years (1999–2008) the total number of recorded cases of AP among adult residents of Russia increased almost 4 times (from 31,500 people in 1999 to 115,530 people . in 2008). An improvement in the technical basis for diagnosis, namely the supply of bone densitometers to medical institutions, which made it possible to measure bone mineral density (BMD) and make a diagnosis of AP, had a significant impact on the frequency of detection of the disease. In 2005, the Russian Association for AP developed clinical guidelines for the diagnosis, prevention and treatment of AP, including glucocorticoid AP, and in 2009 they were revised and supplemented. Recommendations are ranked according to a unified international system of levels of evidence. Despite general recommendations, treating AP in a particular patient is often a difficult task and depends both on the doctor’s interpretation of the patient’s condition and on the patient’s readiness for long-term therapy. There are two main types of AP – primary and secondary, with primary AP being the most common: the ratio of its frequency to the frequency of all possible forms of secondary AP reaches 4:1 [1]. Primary AP is conventionally divided into postmenopausal and senile. Postmenopausal AP is associated with accelerated bone loss in women after the cessation of the menstrual cycle, and is caused by estrogen deficiency. The main reasons for the development of senile AP in individuals of both sexes are a decrease in calcium intake, impaired absorption in the intestine and vitamin D deficiency, which can lead to secondary hyperparathyroidism and, as a result, accelerated bone remodeling. One of the factors influencing the development of senile AP is considered to be a decrease in physical activity in old age. It must be emphasized that during the aging process, the interaction of hormones with growth factors and other cytokines that influence the process of osteoblastogenesis undergoes significant changes, and the activity of many local factors decreases. AP develops gradually and is often clinically detected after fractures, which is the basis for calling it a “hidden epidemic.” It should be noted that the incidence of AP increases with age, therefore, the increase in life expectancy observed in recent decades in developed countries and the associated rapid increase in the number of elderly people, especially women, leads to an increase in the frequency of this disease, making it one of the most important health problems worldwide. world. Providing medical care to patients with primary AP is carried out on an outpatient basis, with the exception of cases requiring surgical treatment of complications of AP - fractures. Treatment and observation of the patient is long-term, over several years, and should be carried out by a primary care doctor - a local therapist or a general practitioner. If secondary causes of the possible development of AP are identified, the patient should be referred for consultation to a specialist (rheumatologist, endocrinologist, etc.). Among diagnostic measures, clinical examination methods come to the fore: studying the patient’s complaints and medical history in order to identify risk factors for AP and risk factors for falls, as well as clinical signs of bone fractures, including vertebral fractures. Identification of the presence of AP in a particular individual includes an assessment of the family history of AP, lifestyle (bad habits, physical activity, nutrition, etc.), the presence of fractures, reproductive history, the presence of diseases and drug therapy leading to the development of AP (Table 1). Falls are an independent risk factor for fractures because... most fractures of the proximal femur and distal forearm occur due to falls (Table 2). Physical examination of a patient with AP includes a general medical examination with measurement of height and weight. A decrease in height by 2.5 cm per year or by 4 cm or more compared to height at 25 years of age may indicate AP complicated by vertebral fractures. If the fracture was recent, local pain in the vertebral area may be noted, and progressive changes in posture may be accompanied by paravertebral pain on palpation and tension of the paravertebral muscles, and limited mobility in the spine. To diagnose AP, various instrumental methods are used: bone radiography and measurement of bone mineral density using bone densitometry. Bone radiography remains the only research method that allows one to evaluate the anatomical features of bones and the structure of bone tissue, as well as various skeletal injuries. One of the disadvantages of radiography in diagnosing AP is the low sensitivity of the method, which makes it possible to detect a decrease in bone mass when the degree of decrease in mineralization reaches 20–40%. Currently, radiography is used to detect or confirm bone fractures of any location. To diagnose osteoporotic fractures of the vertebral bodies, the method of X-ray morphometry of the spine in the lateral projection is used. X-ray morphometric analysis of the vertebral bodies includes measurement of the anterior, middle and posterior heights with the calculation of indices: anterior/posterior index - the ratio of the anterior height of the vertebral body to the posterior; middle/posterior index – the ratio of the average height of the vertebral body to the posterior; posterior/posterior index – the ratio of the posterior height of the body of the vertebra under study to the posterior heights of one or two overlying and underlying vertebrae. To assess deformations, the quantitative method of H. Genant is used [3]. Vertebral body indices of more than 0.8 (80%) indicate a normal configuration of the vertebra, with any index of 0.75–0.79 – a 1st degree of deformity, with 0.6–0.74 – a 2nd degree , and if 0.59 or less – a severe osteoporotic vertebral fracture of the 3rd degree. The OP of the spine is characterized by such types of deformities as anterior or posterior wedge-shaped, unilateral or biconcave deformities, as well as a compression fracture. Indications for referral of patients for X-ray examination include back pain and decreased height to detect osteoporotic vertebral fractures. Currently, the “gold standard” for diagnosis is the measurement of BMD using dual-energy X-ray absorptiometry (DXA), which estimates the amount of mineralized bone tissue in the scanned area (g /cm2). Standard testing methods include densitometry of the lumbar spine and proximal femur (femoral neck and total hip index), since the prevalence of fractures has been shown to correlate with BMD in these areas based on numerous assessment methods. The diagnosis of AP is made in postmenopausal women and men aged 50 years and older by comparing the obtained BMD data with the apparatus’s abstract database (the average value of “peak bone mass” in young healthy people according to the T-criterion) using the WHO recommendation [WHO, 1994] , according to which normal BMD values ​​include indicators above -1SD from the reference base according to the T-criterion, values ​​from -1SD to -2.5SD are classified as osteopenia, deviations below -2.5 SD - as OP, and with the additional presence of one and more fractures – as severe AP. If it is not possible to study the spine and hip, the results of measurements of the distal forearm can be used. Indications for referring patients for densitometry are the presence of risk factors for AP in patients under 65 years of age and to assess the effectiveness of pathogenetic treatment of AP. For the differential diagnosis of primary AP and metabolic diseases of the skeleton, as well as before prescribing antiresorptive therapy, a mandatory study of calcium, phosphorus and alkaline phosphatase in the blood, calcium in daily urine or the ratio of calcium to creatinine in morning urine is recommended. It should be remembered that in primary AP, the level of the above indicators in the blood is within normal limits, but hypercalciuria is possible, especially for the variant of AP with increased bone turnover. In addition, additional laboratory methods can be used, the purpose of which is to establish a diagnosis of the underlying disease, one of the symptoms of which is osteopenia (for example, thyroid-stimulating hormone, parathyroid hormone, 25-hydroxyvitamin D, etc.). To assess the rate of bone turnover, markers of bone formation (osteocalcin OS, carboxy- and aminoterminal propeptides of procollagen type I - PICP, PINP, bone isoenzyme of alkaline phosphatase - bALP), as well as markers of bone resorption (oxy- and deoxypyridinolines - PYR, DPYR, hydroxyproline - OHPr in urine, N- and C-telopeptides of type I collagen molecules cross-linked - NTX, CTX in blood serum or urine, as well as tartrate-resistant acid phosphatase - TRACP in blood plasma). However, at present there is no evidence of the importance of determining the level of bone markers for individual diagnosis of AP and for predicting the risk of fractures in individual patients in clinical practice; they can be used to assess the therapeutic effect of the drug (a decrease in their level by 30% or more when taking antiresorptive therapy is predicted good treatment effectiveness) and improved patient adherence to treatment. Treatment of AP includes both non-drug therapies and pharmacological interventions. Among the first, it should be noted educational programs, giving up bad habits (smoking, alcohol abuse, caffeine, heavy physical activity), physical education (walking, gymnastics, isometric exercises, swimming), fall prevention (vision correction, treatment of concomitant diseases, assessment and change home environment, movement pattern training, balance training), patients with vertebral fractures should be recommended to wear rigid or semi-rigid corsets for up to 4–6 hours during physical activity, because they reduce the severity of pain. With AP, such types of loads as jumping and strength exercises, sudden bends and rotations of the body should be excluded. Drug treatment of AP is a difficult task, since it is diagnosed quite late, when there may already be a history of fractures of various locations. Treatment must be long-term, since the effect may take many months to appear. In this regard, there is a constant search for highly effective and inexpensive drugs. The goal of therapy is to slow down and, if possible, stop bone loss, prevent bone fractures, improve the patient's condition, reduce pain, and improve his quality of life. Today, the range of drugs for the treatment and prevention of AP has expanded significantly; their use reduces the risk of fractures from 30 to 70%. The drugs of first choice for pathogenetic therapy are drugs of the bisphosphonate (BP) class and strontium ranelate. The action of BP is based on reducing the rate of bone turnover due to its effect on osteoclasts - cells that destroy old bone - while maintaining bone microarchitecture and increasing bone mineral density (BMD). One of the drugs in the BF class is alendronate, which has been widely used in clinical practice throughout the world for almost 15 years. When treated with alendronate, resorption processes by osteoclasts are suppressed and bone metabolism processes are restored to premenopausal levels and prevents microarchitectural disorders and bone loss. The processes of bone metabolism remain stable during long-term treatment with alendronate for 10 years, while the accumulation of the drug in the bone does not lead to excessive suppression of bone turnover, but, on the contrary, demonstrates that bone turnover remains at premenopausal levels, and bone quality remains normal throughout the treatment period . Data from pharmacokinetic studies have confirmed that the effectiveness of BP on bone mass and strength depends on the cumulative dose of these drugs. Thus, the same amount of alendronate is absorbed with a single dose of 70 mg once a week. or 10 mg 7 times/week. The effectiveness of alendronate in patients with AP has been proven in several randomized clinical double-blind placebo-controlled studies (RCTs) [4,5,6]. Taking alendronate showed high efficiency: it significantly reduced the incidence of vertebral fractures by 47%, hip fractures by 51–56%, and forearm fractures by 48% [5,7]. Currently, alendronate is the first drug that has a 10-year study duration that assessed the dynamics of BMD in groups of patients who took alendronate throughout this period or were switched to placebo after the first 5 years of active therapy. In women who continued to receive 10 mg/day. alendronate, there was a gradual increase in spine BMD to 13.7% (p<0.001), and hip BMD to 6.7% (p<0.001) relative to the initial level. As a result of alendronate administration, the level of bone turnover markers decreased to premenopausal levels, which remained stable over the entire 10-year period without signs of oversuppression. Compared with the study group, individuals who took placebo over the past 5 years showed a decrease in total hip BMD (–2.4%; 95% CI –2.9%; –1.8%; p<0.001) and lumbar spine (–3.7%; 95% CI –4.5%; –3.0%; p<0.001), however, mean BMD values ​​remained above baseline at study entry. At 5 years, the overall risk of peripheral fracture was not significantly different between groups (RR 1.00; 95% CI 0.76, 1.32). Those who continued alendronate therapy had a significantly lower risk of clinically significant vertebral fractures: for example, in the placebo group they occurred in 5.3% of patients, and in the alendronate group – in 2.4% (OR 0.45; 95% CI 0.24; 0.85). For fractures detected by X-ray morphometry of the spine, such a pattern was not found (11.3 and 9.8%, respectively; RR 0.86; 95% CI 0.60, 1.22). A small number of iliac biopsies did not reveal any qualitative bone pathology. In summary, this study showed that stopping treatment after 5 years does not significantly increase the risk of fractures, but women at high risk of clinical vertebral fractures should continue treatment beyond 5 years [6]. When taking oral bisphosphonates, much attention is paid to adverse events (AEs) associated with damage to the gastrointestinal tract. It should be noted that during the studies, the frequency of all adverse events when taking 10 mg of alendronate per day did not exceed that in the placebo group [5]. Currently, all over the world, due to the problem of treatment compliance, preference is given to another dose of the drug 70 mg 1 time/week. RCTs have shown that this dosage of alendronate provides therapeutic equivalence to a daily dose of 10 mg of the drug, while at the same time better tolerability and ease of use [8–10]. Thus, the increase in BMD was 6.8 and 7.4%, respectively, in the spine, 4.1–4.3% in the hip. A two-year follow-up of patients receiving various doses of alendronate showed that the incidence of fractures in the 70 mg group once a week. was 7.3%, and in the group 10 mg/day. – 7.0% (p>0.05). There is clear evidence of a reduction in fracture risk with alendronate 10 mg daily, and the lack of difference in fracture incidence at both doses, comparable increases in BMD, and similar changes in bone turnover marker levels suggest a similar effect on fracture risk at these dosages. The biopsy material showed no signs of osteomalacia when taking both doses of the drug. In a comparative study, it was shown that the frequency of gastrointestinal AEs (esophagitis, erosion, hemorrhage, reflux, gastritis, stomach ulcer, etc.) in groups receiving different doses of alendronate was similar, i.e. an increase in a single dose of 7 times did not increase the risk of developing AEs [10,11]. The RI RAMS conducted a study of the effectiveness and safety of alendronate 70 mg/week. in an open-label, one-year controlled study [11]. After a year of therapy, a significant increase in BMD in the spine and femoral neck was obtained in patients receiving alendronate compared to the comparison group (p=0.00001 and p=0.030, respectively). When assessing the number of patients with a significant increase in the MPC in the spine and the proximal thigh department, it was revealed that in the group that received treatment with alendronate, 85.7% of patients had an increase in more than 2% in the spine and 42.8% of people - in the field of the hip neck, and 38.8% had a significant increase in both areas of measurement, which was significantly higher than in the comparison group (p = 0.01). At the same time, the increase in MPCT more than 6% in the spine was found in 53% of women who received alendronate, and in the neck of the thigh - an increase of more than 3% - in 30.6%. In addition, when taking alandronate, it was reliably more women who positively responded to treatment than women whose effect was absent (p <0.001). Our study showed high efficiency of alendronate at a dose of 70 mg 1 time/week. In the treatment of primary OP in women in postmenopausa: it had a positive effect on the MPC, reduced the pain syndrome and, as a result, reduced the restriction of the physical activity of patients. It is noted quite good tolerance of the drug, side effects in the treatment group were comparable to those in the comparison group. An analysis of the action of alendronate showed that it has a path for the 12 -month period after the end of treatment in relation to the MPC of the spine. Alendronate is effective in both men and women, for the prevention and treatment of glucocorticoid (Civil Code) OP both in relation to the increase in the IPC and a reduction in risk of fractures. The fundamental evidence of the effectiveness of the alendronate was obtained in a randomized clinical study with a placebo control, in which men and women (n = 477) with newly prescribed Civil Code (34% of patients) or with Civil Code of therapy that lasted more than 4 months. (66% of patients), were under observation of more than 48 weeks. Positive effects of treatment for 12 months. At the MPC, they were statistically reliable in the lumbar spine and the hip neck. It is noted that in the Alendronate group of new vertebral fractures during the observation period, there were less than the placebo group (2.3 and 3.7%, respectively, P> 0.05). Subsequently, observation of 208 patients showed the effectiveness of therapy with alendronate during the 2nd year and a significant decrease in the number of new vertebral fractures in the Alendronate group (0.7%) compared to the placebo group (6.8%; p = 0.026) [ 13]. Alendronate must be taken on an empty stomach immediately after lifting from bed, the tablet must be washed down with 1 cup (180–240 ml) of pure water, and after receiving you should be in an upright position (sitting or standing) for at least 30 minutes. BF can cause side effects associated with the defeat of the gastrointestinal tract, as well as headache, muscle pain and bones, a decrease in calcium and phosphorus in the blood serum, in rare cases - a rash and erythema. With an overdose of BF - hypocalcemia and hypophosphatemia, gastrointestinal tract disorders. Compliance with recommendations for taking the drug significantly reduces the risk of gastrointestinal nia. Contraindications to their purpose: hypersensitivity to the drug, stricture and esophagus ahalazia, severe renal failure (creatinine clearance below 35 ml/min.), Hypocalcemia, pregnancy and breastfeeding, children's age, severe hypoparastic, calcium malabsorption. It should be remembered that taking drugs affecting pathogenesis of the OP should take place against the background of sufficient intake of calcium and vitamin D with food or in the form of drugs. Active metabolites (alfacalcidol and calcitriol) can be used as a vitamin D donator, the combined use of them with BF leads to an increase in the MPC of the spine and the hips of the thigh, a decrease in the risk of falling and peripheral bones [14].

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