How to treat postmenopausal osteoporosis? Postmenopausal osteoporosis: how to prevent bone fracture? Basic principles of prevention and treatment

Osteoporosis is a systemic skeletal disease characterized by a decrease in bone mass, disruption of bone microarchitecture with a subsequent increase in bone fragility and an increased risk of fractures. Bone loss occurs gradually and is often diagnosed only after fractures. As women live longer, their risk of developing osteoporosis and fractures increases.

In adult individuals, the mineral composition of bone tissue is determined by several factors: heredity, physical activity, dietary habits and hormonal status. A few years after reaching peak bone mass, bone loss begins at the age of 30-35, which is a universal phenomenon of human biology that occurs regardless of gender, race, profession, habitual activity, economic development, geographic area of ​​residence and historical era. The average bone loss in a woman is approximately 1% per year relative to peak bone mass during reproductive age. This process accelerates within the first five years after menopause.

Primary or involutional osteoporosis is a systemic lesion of the skeleton of elderly people (50 years and older).

Primary

Primary osteoporosis develops pathogenetically in two clinical variants:

• postmenopausal;
• senile or senile

Risk factors for primary osteoporosis are often hereditary and also associated with family and/or personal history:

• elderly age;
• graceful, short women with a fragile physique and fair skin, especially from among the residents of Northern Europe and Asia;
• indications of fractures in the family history;
• later menarche (after 15 years);
• early menopause (before 50 years);
• oligo- or amenorrhea during reproductive age;
• anovulation and infertility;
• more than 3 pregnancies and births during reproductive age;
• long-term lactation (more than 6 months)

Secondary

Secondary osteoporosis is a multifactorial disease in which the following factors play a role:

• endocrine (hyperthyroidism, hypoparathyroidism, hypercortisolism, diabetes, hypogonadism);
• malnutrition and calcium deficiency in the diet;
• excessive intake of alcohol, nicotine, coffee (more than 5 cups per day);
• long-term use (over 4 weeks) of corticosteroids, heparin, anticonvulsants;
• genetic factors: incomplete osteogenesis, low peak bone mass;
• other factors: chronic renal failure, decreased absorption of calcium in the intestine, prolonged immobilization, physical inactivity.

The incidence of primary osteoporosis in developed countries is 25-40% with a predominance of this disease among white women. By age 70, 40% of white women have a history of at least one osteoporotic fracture. Among black African women, the incidence of osteoporosis is 11-12%. Among Moscow residents, osteoporosis of the lumbar vertebrae in the population of women 50 years and older was detected in 23.6%. The frequency of bone fractures in women in the age group 50-54 years increases 4-7 times compared to men of the same age and continues to increase in older age groups. Among women who have suffered bone fractures, osteoporosis is found in 70% of cases.

The processes of formation and resorption constantly occur in bone tissue. In the processes of its formation, osteoblasts play a leading role, and osteoclasts play a leading role in resorption (Fig. 14). During the period of reaching peak bone mass, formation processes prevail over resorption processes. Loss of bone mass in menopause is accompanied primarily by bone damage with a predominance of spongy substance (vertebral bodies, distal parts of the forearm bones, etc. (Fig. 15).

Senile osteoporosis develops after 70 years and is characterized by predominant damage to long bones with an increase in femoral neck fractures. At the same rate of bone loss, the severity of its deficiency in older women primarily depends on the magnitude of its peak mass. Deficiency of sex hormones in menopause can have both direct and indirect effects on the condition of bone tissue.

Pathogenesis

The pathogenesis of osteoporosis in estrogen deficiency conditions is characterized by:

• increased sensitivity to parathyroid hormone due to an increase in the content of parathyroid hormone receptors in bone tissue and increased resorption;
• a decrease in the level of calcitonin, which stimulates the synthesis of calcitriol in the kidneys and, accordingly, a decrease in calcium absorption;
• increased Ca excretion in urine;
• decreased absorption of Ca in the intestine;
• decreased hydroxylation of vitamin D in the kidneys;
• insufficient supply of calcium to bone tissue

The direct effect of exo- and endogenous sex hormones (estradiol, progesterone and testosterone) on bone tissue occurs through their binding to specific receptors on osteoblasts. Thus, spongy bone tissue is a kind of target organ for sex hormones.

The processes of bone tissue formation and resorption are also associated with the influence of a number of local factors that can have an inhibitory and stimulating effect on osteoblasts and osteoclasts. Thus, proliferation, differentiation and general activity of osteoblasts (collagen synthesis, bone matrix formation) are stimulated by transforming growth factor, insulin-like growth factors (somatomedins), α-microglobulin, osteopectin and other factors. Stimulation of proliferation, differentiation and resorptive activity of osteoclasts is carried out by prostaglandins E2, interleukins-1 and -6, vasoactive intestinal peptide, interferon, tumor necrosis factor, lymphotoxins, macrophage colonizing factor, etc. Age-related loss of part of the spongy layer disrupts the structure of the bone and contributes to the occurrence of fractures.

The generally accepted hypothesis about the mechanism of development of osteoporosis is based on the idea of ​​the protective effect of estrogens in relation to bone tissue. A decrease in the level of estrogenic influences of various etiologies makes bone tissue more sensitive to the absorbable influence of parathyroid hormone and/or vitamin D3. The protective effect of estrogen is realized through calcitonin, the secretion of which is stimulated by estrogen. In this regard, in postmenopause, the need for Ca increases, to maintain the balance of which it is necessary to replenish the daily requirement in the amount of 500 to 1500 mg. In accordance with changes in bone density, when it decreases by 10%, the risk of fractures of the vertebral column and proximal femur increases by 2-3 times.

The decrease in the density of the spongy substance of the vertebrae in early postmenopause is directly related to the initial volume of bone tissue: the higher the density of the latter, the greater the magnitude of the absolute loss. The loss of bone tissue is especially great in early postmenopause, when the mass of the spongy substance of the vertebral processes decreases by 5% per year, and the cortical layer - by 1.5%.

In the development of age-related AP, parathyroid hormone plays the role of a mediator. Changes in mineral homeostasis and bone tissue deficiency develop against the background of decreased function of the parathyroid glands, endocrine renal function and other manifestations of age-related involution.

Clinical picture

Osteoporosis develops gradually and can go undetected for a long time. The manifestation of its characteristic symptoms reaches a maximum after approximately 10-15 years (Fig. 16).

The main clinical symptoms are pain in the bones, especially often in the bones of the lumbar or thoracic spine, which can transform into a picture of radiculitis. There is a slow decrease in height with corresponding changes in posture, progressive limitation of motor activity of the spine, and loss of body weight.

Patients are often treated for a long time without sufficient effect for “radiculitis”, erroneously diagnosed multiple myeloma, metastases of a malignant tumor, and multiple spinal injuries.

Fractures are the late and most striking manifestation of osteoporosis. Fractures often occur at home when falling from a height. The most common fractures are the radius and vertebrae. Particularly tragic are hip fractures, mortality in which is observed in 20-25% of cases during the first six months, and severe disability occurs in 40-45% of cases.

Diagnosis of osteoporosis

1. Study of anamnesis
2. Determination of body weight and height
3. Determination of bone mineral density

Single-photon densitometers Typically used to measure bone mineral density in the hand, distal forearm, or lower leg. Equipment of this class is easy to use, mobile, small in size and light in weight, and does not require a separate room or lengthy operator training. The duration of one study (without data analysis) is 5-10 minutes. Single-photon densitometers can be used for screening studies.

However, it should be taken into account that mineral density indicators of the distal parts of the bone skeleton in a significant number of peri- and postmenopausal women may differ little from the norm and do not always reflect age-related metabolic changes.

Two-photon X-ray densitometry is based on the use of a modification of two-photon radionuclide densitometers. The latest models make it possible to examine any bone and the entire skeleton in two or more projections. The examination time is significantly reduced by increasing the detectors. The duration of the study is 1-15 minutes, depending on the immediate task and model of the device.

Quantitative computed tomography. The main disadvantages of this method are associated with the difficulties that arise when studying small bones due to the so-called “partial volume effect” and with the relatively large total radiation dose during long-term dynamic observations.

Ultrasound densitometry. It has advantages when examining postmenopausal women, since against the background of estrogen deficiency, trabecular bones are primarily affected. The object of study is usually the heel bone.

X-ray diagnostics- informative for loss of bone tissue mass over 30%.

To assess the activity of the processes of bone formation and resorption, as well as to dynamically assess the effectiveness of the treatment, they resort to determining biochemical markers.

Prevention

Preserving bone mass is an easier task than restoring it. In this regard, the prevention of osteoporosis, which should be carried out throughout a woman’s life, is of particular importance. In this case, serious attention should be paid to the formation of peak bone mass and the creation of a skeleton with maximum strength by the period of puberty and the prevention of postmenopausal and age-related deficiencies in the mineral composition of bone tissue.

Since the genetic determinants of bone tissue are predetermined, the main attention should be paid to environmental factors, the period of bone growth in adolescence, pregnancy, lactation and perimenopause.

• nutritious diet with adequate intake of calcium-containing foods;
• physical activity, “ability to fall”;
• elimination of bad habits (smoking, coffee, alcohol);
• maintaining a regular menstrual cycle during reproductive age;
• active advertising of preference for dairy drinks over carbonated ones;
• timely identification of risk groups;
• prescription of vitamin D and calcium supplements, incl. and in women over 70 years of age;
• prevention of a progressive decrease in peri- and postmenopausal bone loss is also achieved through the administration of sex hormones

It is generally accepted that a postmenopausal woman should receive 1200-1500 mg of calcium per day, which is preferably compensated for by a nutritious diet. The most natural source of calcium is dairy products. In cases of enzyme deficiency, milk allergy or blood lipid problems, calcium tablets can be used. Vitamin D stimulates the absorption of calcium in the intestine, reduces the activity of parathyroid hormone and increases the activity of bone formation processes.

Treatment

Due to the fact that the pathogenesis of postmenopausal osteoporosis is quite complex and ambiguous, the treatment of this contingent of patients aims to block the processes of bone tissue resorption and, at the same time, activate the processes of bone formation.

The following are used to treat osteoporosis:

1. Sex hormone preparations:
   • estrogens + gestagens, in the form of mono-, two- and three-phase preparations;
   • estrogens + androgens
2. Calcitonin
3. Bisphosphonates
4. Vitamin D

I. The mechanism of the protective effect of estrogens on bone tissue:

• activation of calcitonin synthesis;
• blockade of parathyroid hormone activity by reducing its synthesis or reducing the sensitivity of osteoclasts;
• decreased sensitivity of bone tissue to the absorbable effect of vitamin D 3 metabolites;
• activation of the processes of hydroxylation of vitamin D 3 in the kidneys and its conversion into the active form 1,25-dihydroxycholecalciferol;
• increased absorption of calcium in the intestine;
• reduction of the catabolic effect of thyroxine due to increased synthesis of thyroglobulin

Optimal doses of estrogen for the prevention and treatment of osteoporosis:

• estradiol valerate 2 mg per day;
• conjugated estrogens - 0.625 mg

The protective effect of gestagens on bone tissue manifests itself as a direct effect through specific receptors on osteoblasts and indirectly by blocking glucocorticoid receptors and reducing their inhibitory effect on bone tissue.

Contraindications to hormone replacement therapy for osteoporosis:

• tumors of the uterus, ovaries and mammary glands;
• uterine bleeding of unknown origin;
• acute thrombophlebitis;
• acute thromboembolic disease;
• thromboembolic disorders associated with estrogen use;
• renal and liver failure;
• severe forms of diabetes mellitus

During replacement therapy, blood pressure monitoring, oncocytological examination, genital ultrasound and mammography once a year are required every three months, and regular participation of patients in mini-lectures and group discussions about the benefits and safety of hormone therapy.

Postmenopausal hormone therapy remains the treatment of choice for the prevention and treatment of postmenopausal osteoporosis.

Hormone replacement therapy has a positive effect on bone mass. A placebo-controlled study showed that after three years of continuous treatment, the mineral composition of the bones of the forearm was 9% higher than that of women in the placebo group (Fig. 17).

In order to prevent osteoporosis, the prescription of hormonal drugs is indicated for a period of time during 5-8 years of postmenopause. When carrying out replacement therapy, not only does bone loss stop, but also the mineral density of bone tissue increases both in the spine and, importantly, in the femoral neck.

II. Calcitonin(CT) is prescribed in cases of verified osteoporosis in the presence of contraindications to the use of sex hormones or if the patient has a negative attitude towards them.

The main biological effect of CT:

• inhibits bone resorption by inhibiting the activity and reducing the number of osteoclasts;
• has a pronounced analyzing effect for bone pain through interaction with P-endorphins;
• promotes the reparative formation of bones during fractures, blocking the breakdown of collagen;
• increases the supply of calcium and phosphorus to the bone

The formation of CT in the body can be stimulated by the administration of testosterone, estrogens, gestagens and combined estrogen-progestogen drugs.

In clinical practice, synthetic CT is widely used, which is 20-40 times more active than natural one (Table 4).

Patients should receive 600-1200 mg of calcium daily in addition to taking CT. Adverse reactions are observed in 10-30% of cases (nausea, dizziness, polyuria, chills, hot flashes).

III. Bisphosphonates(xidifon) - active analogues of pyrophosphate, which blocks bone resorption processes and is prescribed at a dose of 5-7 mg/kg body weight for 14 days, one course of treatment every 3 months. According to biochemical and densitometric studies, the cessation of bone resorption is determined. In high doses, bisphosphonates can block bone mineralization (!).

IV. Vitamin D 3. Its biological effect is:

• stimulation of calcium and phosphorus absorption in the intestines;
• simultaneous impact on the processes of resorption and formation of bone tissue through blockade of parathyroid hormone secretion;
• increasing the concentration of calcium and phosphorus in the matrix and stimulating its maturation;
• influence on growth factors, which helps increase bone strength

The dose of vitamin D 3 is adjusted during the first two weeks under the control of serum calcium levels. Subsequently, monitoring of calcium balance is necessary every 2-3 months. Vitamin D intake is indicated for life, as it can serve as an effective way to prevent senile osteoporosis.

Activation of bone formation processes can be achieved by administering sodium fluoride, anabolic steroids and active forms of vitamin D. Sodium fluoride at a dose of 75 mg with the addition of calcium has a long-lasting anabolic effect on bone tissue. Anabolic steroids can be used for severe osteoporosis in older people, however, side effects (hirsutism, decreased voice, increased atherogenic lipid fractions, etc.) limit their use for a long time.

Despite the variety of methods for the prevention and treatment of postmenopausal osteoporosis, the most reasonable method of intervention for the purpose of prevention and pathogenetically based treatment is the use of sex hormones.

A serious argument in favor of prescribing hormonal replacement treatment to women of any age for the purpose of preventing and treating hormone deficiency conditions is evidence of a 50% reduction in the risk of fractures of the forearm and femoral neck after treatment carried out during the first 5-7 years since menopause.

Due to the important medical and social significance of the problem of postmenopausal osteoporosis and the significant material costs associated with the treatment and rehabilitation of patients with osteoporosis and bone fractures in modern society, screening examinations to identify risk groups.

• Carrying out the first screening at 50 years old allows us to distinguish three degrees of risk, justify the need for hormonal effects and clarify the time of re-screening;
• Screening at age 70 makes it possible to more accurately predict a woman's risk level by age 80

Why are women over 50 prone to fractures? It happens that after an injury, the doctor informs the patient about the fragility of the bone, prescribing calcium supplements. Many women do not even realize that postmenopausal osteoporosis (PMO) is to blame.

In the article we will learn in detail about what kind of pathology this is and how it can be prevented.

Among all forms of osteoporosis, the incidence of postmenopausal osteoporosis is 85%. According to statistics, every fourth woman over 50 years of age has a history of one (or more) serious fracture.

It is believed that age-related hormonal changes and the “turning off” of the ovaries (cessation of menstruation) leads to estrogen deficiency. According to numerous studies, within twenty years after the onset of menopause, developing osteoporosis provokes a decrease in the mass of trabecular (wrist, tarsus) tissue by 50% and cortical tissue (80% of the skeleton consists of it) by 30%. The bones of the vertebrae are especially vulnerable. When they become loose, senile kyphosis occurs, which is often combined with a “dower’s hump.”

Interesting to know! The widow's hump (photo below) is an accumulation of fat in the projection of the seventh cervical vertebra. Pathology received its interesting name back in the Middle Ages, famous for the Crusades, feudalism and the Hundred Years' War. As a rule, “older” women no longer had husbands, because they often died very early, before reaching fifty years of age.

The risk of fracture mainly depends on the initial mass of the bone. If a woman had low bone mass at age 30, postmenopausal thinning will significantly exceed the chances of surgical trauma. So, even with a slight fall or spontaneously, you can “earn” a heavy one.

To find out detailed information about the effect of female sex hormones on bone structure, watch the video in this article.

Preventive measures

Doctors cite disappointing statistics regarding osteoporosis. Bone loss ranks fourth in the world in severe pathologies, behind respiratory and cardiovascular diseases, and oncology.

The basis for preventing PMO, and therefore fractures, is to maintain bone density. For your attention, table No. 1 “How to prevent postmenopausal osteoporosis? Recommendations".

It is also worth carrying out secondary prevention of PMO: correction of estrogen deficiency conditions caused by amenorrhea, artificial or surgical menopause, and chemotherapy. At the same time, it is necessary to think about preventing falls - using a cane or wheelchair.

It is also not advisable to go outside in wet or damp weather, or in icy conditions; wear shoes with rubberized anti-slip soles. Listen to your doctor's recommendations regarding wearing special protectors and corsets.

Diagnosis of osteoporosis

Today, identifying osteoporosis is not a problem. To do this, just visit a therapist and take the necessary referrals.

Hardware methods for studying bone tissue to diagnose menopausal osteoporosis:

1. Densitometry. This is a painless and safe procedure that is carried out relatively quickly - from 10 to 30 minutes, and when studying peripheral parts, a few minutes are enough. The principle of operation of the equipment is based on exclusive geometric scanning, which allows high-precision assessment of the condition of bone tissue using a fan-shaped beam.

The patient can remain in clothing if it is loose enough and there are no metal elements on it. Experts recommend that all women over 45 years of age undergo densitometry once every 24 months to study the dynamics of skeletal density. The average price of diagnostics in Moscow ranges from 1,200 to 2,000 rubles.

1. X-ray diagnostics. This research method is considered insufficiently informative and detects osteoporosis only when bone loss is 40 percent or more. But it is worth noting the positive aspects of X-ray diagnostics, in particular, its low cost, accessibility and speed of image acquisition.
2. Examination using CT and MRI. Computed tomography (CT) also relies on R-irradiation, but it is more accurate than radiography. The results of the study will help to find out the condition of not only bone tissue, but also cartilage, ligaments and muscles. Using a magnetic resonance imaging (MRI) scanner, you can obtain a three-dimensional image of the area under study thanks to outgoing radio signals generated by the vibration of hydrogen atoms in a magnetic field.

There are also laboratory methods for testing blood and urine, which are prescribed to assess phosphorus-calcium metabolism in the body.

Table No2. Laboratory methods for diagnosing PMO:

Modern methods of treating osteoporosis

The main goal that must be achieved is to reduce the incidence of fractures (even the absence of them) and prevent further progression of the disease.

In order for the patient to choose the most appropriate therapy, she may need to consult the following specialists:

• endocrinologist - if there is a malfunction of the thyroid, parathyroid glands, a history of diabetes mellitus or Ishenko-Cushing syndrome;
• oncologist - if there is a suspicion of metastatic lesions of the skeleton;
• in case of numerous and frequent fractures, consult an orthopedist;
• geneticist – if the patient has a genetic predisposition to osteoporosis or already has diseases such as osteogenesis imperfecta, desmogenesis, Marfan syndrome;
• gastroenterologist – for chronic liver disease (primary biliary cirrhosis), disorders of digestion, transportation and absorption of nutrients (malabsorption), after removal (resection) of part of the stomach;
• nephrologist - if there is a history (or were identified during the diagnosis of osteoporosis) of impaired renal function (chronic renal failure, glucose-phosphate-amine diabetes, renal tubular acidosis);
• gynecologist - if estrogen deficiency conditions are detected;
• a consultation with a hematologist is recommended in cases of suspected presence of a disease of the hematopoietic organs (generalized plasmacytoma, “marine anemia”, mast cell leukemia);
• consultation with a rheumatologist if osteoporosis is accompanied by rheumatoid arthritis, Libman-Sachs disease and ankylosing spondylitis.

Drug treatment

It is not possible to completely get rid of osteoporosis, so the patient should learn to live with this disease and, with the help of therapy, stop the further development of the pathology.

Important! The instructions for the drug should not be considered as a call for self-therapy!

In postmenopause, it is most often carried out according to the following scheme:

1. Biosphosphonates. The drugs will stop the destruction of the skeleton, thereby promoting the formation of new bone tissue. Biosphosphonates are absolutely safe for the human body and have virtually no side effects. According to studies, taking the drugs reduces the incidence of fractures by 50%.
2. Calcium preparations. The one we all know best is calcium gluconate. It is prescribed to all patients suffering from bone fragility. Calcium preparations are not friendly with biosphosphonates, so the interval between doses should be at least four hours.
3. Vitamin D. Vitamin D preparations stimulate the work of osteoblasts (these are cells necessary for the “building” of bone) and improve the mineralization of hard connective tissue. Therefore, it is generally accepted that this group of medications is involved in the healing process of fractures and the formation of microcalluses, which is a necessary condition for increasing the strength of the skeleton.
4. Correctors of bone and cartilage tissue metabolism. One of the common drugs belonging to this pharmacological group is Miacalcic. Treatment with medication will help compensate for the deficiency of calcitonin. The drug inhibits the production of parathyroid hormone and also helps regulate calcium metabolism and bone metabolism. If a fracture does occur, then the medication Miacalcic taken in this case will have an analgesic effect.

Sometimes doctors prescribe hormone replacement therapy. Treatment is usually prescribed to postmenopausal women 45-50 years old. At older ages, hormones are not prescribed due to the high risk of developing serious side effects, such as venous thrombosis or breast cancer.

Traditional methods of treatment

Attention! Before describing traditional methods for osteoporosis, it should be pointed out that using them alone as treatment will never save you from the “fragile” problem. This type of therapy is recommended to be used in parallel with medications, after consulting with your doctor in advance!

Lemon and chicken eggs

Squeeze the juice from ten lemons and pour it over six eggs. It is advisable to use enamel dishes (saucepans) for this, cover the “mixture” with a lid and place in a cool place. Wait until the eggs (along with the shell) are completely dissolved (about a week will pass).

Add 300 grams of honey and a glass of cognac to the resulting thick mass. Mix everything. The “homemade preparation” is stored in the refrigerator, take a teaspoon once a day before meals.

You can also treat osteoporosis using eggshells. It is advisable to use an egg from a domestic chicken that has walked “at will.” Wash the shells thoroughly, dry, and crush with a rolling pin.

Take the powder every morning before breakfast, the amount is on the tip of a knife. Treatment is carried out for a month, then take a break for three months and, if necessary, you can start therapy again.

Onion soup

The dish is prepared very quickly, simply, and is also inexpensive. To do this, you need to take two medium-sized onions, wash them with the husks (then remove them and wash them again), chop them finely and fry them on high speed until golden brown.

Pour a liter of water into a saucepan, throw in the fried onions and peels, and cook for fifteen minutes. Let it brew for several hours. Remove the husks and divide the rest into three equal portions.

Consume each serving in one day (preferably in one dose). Total - three days. Then continue the procedure. The course of treatment is one month.

As we found out, menopausal osteoporosis is not such a harmless disease. Early diagnosis, prevention and compliance with all medical prescriptions will allow you to avoid both minor and severe fractures in the future, for example, a fracture of the vertebra or hip joint.

Postmenopausal osteoporosis is a skeletal disease manifested by increased bone fragility and a tendency to fractures against the background of age-related decline in ovarian function.
A decrease in skeletal mass and bone strength begins already at 35-40 years of age. After the cessation of menstruation (monthly uterine bleeding associated with the physiological rejection of the endometrium - the inner layer of the uterine mucosa), this process accelerates significantly, which is associated with insufficient formation of estrogens - female sex hormones.
With the development of severe postmenopausal osteoporosis, the most common fractures are vertebrae, forearm bones and femoral neck.

Symptoms of postmenopausal osteoporosis

For a long time, osteoporosis occurs without clinical manifestations. It is only after significant bone loss that the following symptoms occur:

• back pain (in the lumbar and sacral area), aggravated by walking, turning the body, lifting heavy objects;
• feeling of heaviness in the spine between the shoulder blades, fatigue;
• pain in the pelvic bones (girdle of the lower extremities), in the bones of the legs;
• compression fractures of the vertebrae (the height of the vertebral body decreases), fractures of the radius (the bone between the wrist and the elbow joint), ankles (tibia bones), hip bones, occurring after a slight load or a slight fall or for no reason at all;
• poor posture, curvature of the spine, decreased height (sometimes by several centimeters per year).

Causes

Causes of postmenopausal osteoporosis:

• decrease in the amount of estrogens (female sex hormones), which regulate the processes of restoration and renewal of bone tissue, are involved in the metabolism of calcium (a mineral necessary for bone strength);
• poor nutrition (lack of dairy products, vegetables, herbs, legumes, fish in the diet, excess fat, easily digestible carbohydrates, salt, etc.);
• decreased physical activity.

• age over 65 years;
• Caucasian race;
• hereditary predisposition (osteoporosis or frequent fractures in relatives);
• long-term use of glucocorticoids (medicines - adrenal hormones and their analogues);
• forced immobility (for example, after a cerebrovascular accident - stroke), prolonged bed rest for various diseases;
• low body weight;
• early onset of menopause (last menstruation (monthly uterine bleeding associated with physiological rejection of the endometrium - the inner layer of the uterine mucosa) before the age of 45 years);
• previous gynecological diseases (infertility, removed ovaries, scanty or absent menstruation, etc.);
• smoking;
• Excessive caffeine consumption (coffee, strong tea, cola, etc.)
• alcohol abuse.

Diagnostics

• Analysis of the medical history and complaints (presence of pain in the spine and bones, “accidental” fractures, long-term use of any medications, dietary habits, etc.).
• Analysis of hereditary history (whether relatives suffered from similar diseases, frequent fractures, etc.).
• Analysis of gynecological history (past gynecological diseases, surgeries, number of pregnancies, abortions, etc.).
• Analysis of menstrual function (at what age did the first menstruation begin (monthly uterine bleeding associated with the physiological rejection of the endometrium - the inner layer of the uterine mucosa), what is the duration and regularity of the cycle, how long ago menstruation stopped, etc.).
• Dual-energy X-ray absorptiometry (DXA) is an X-ray method for studying the density of various parts of the skeleton (most often the spine, forearm bones and femur), which has high accuracy and allows you to diagnose osteoporosis in the early stages (with still minor bone loss).
• Biochemical blood test (determination of blood concentrations of calcium, phosphorus, sodium, potassium, chlorine, protein, creatinine, urea, alkaline phosphatase, etc.).
• Analysis of 24-hour urine for calcium concentration.
• Determination of biochemical parameters (markers) of bone damage. The analysis, on the one hand, shows the amount of bone breakdown products, and on the other, the amino acids and enzymes involved in its construction. Depending on the ratio of these markers, we can conclude that the processes of bone breakdown (resorption) predominate over its restoration in osteoporosis.

Treatment of postmenopausal osteoporosis

• A diet enriched with dairy products, seafood, and legumes.
• Physiotherapy.
• Wearing corsets or special braces that reduce the risk of fractures.
• Taking calcium and vitamin D supplements.
• Hormone replacement therapy with sex hormone analogs (estrogens, as well as their combinations with other hormones).
• Taking medications that slow down bone destruction (bisphosphonates, calcitonins, etc.).
• Taking drugs that enhance bone formation (fluorides, anabolic steroids, analogues of parathyroid hormones, androgens, etc.).

Complications and consequences

• Constant bone pain.
• Bone fractures due to heavy lifting, slight falls, bruises, awkward movements, that is, with minimal trauma or no apparent reason at all.
• Rachiocampsis.
• Reduced growth – “trampling”, sometimes up to 4 cm per year.
• Decreased quality of life.

Prevention of postmenopausal osteoporosis

• Balanced nutrition, enriching the diet with foods containing calcium (dairy products, canned fish, nuts, seafood, vegetables, leafy greens).
• An active lifestyle, physical education, regular exercises in accordance with age standards.
• Additional intake of calcium and vitamin D during special periods of life (in childhood, during pregnancy and lactation, during postmenopause (lack of menstruation (monthly uterine bleeding associated with physiological rejection of the endometrium - the inner layer of the uterine mucosa) against the background of age-related decline ovarian function)).
• Quitting bad habits (smoking, alcohol).
• Moderate caffeine consumption (coffee, tea, chocolate, cola, energy drinks).
• Dosed exposure to the sun.
• Timely and complete treatment of gynecological diseases, as well as conditions associated with deficiency or imbalance of hormones in the body.
• Regular visits (2 times a year).

• Authors

  1. Gynecology: National Guide / Ed. V. I. Kulakova, G. M. Savelyeva, I. B. Manukhina. - “GOETAR-Media”, 2009.
  2. Gynecology. Textbook for universities / Ed. acad. RAMS, prof. G. M. Savelyeva, prof. V. G. Breusenko. - “GOETAR-Media”, 2007.
  3. Practical gynecology: A guide for doctors / V.K. Likhachev. - Medical Information Agency LLC, 2007.
  4. Gynecology. Textbook for students of medical universities / V. I. Kulakov, V. N. Serov, A. S. Gasparov. - "Medical Information Agency LLC", 2005.
  5. New concept in the treatment of postmenopausal osteoporosis (literature review) / S. V. Yureneva. - magazine “Attending Physician”, No. 05, 2010.
  6. Postmenopausal osteoporosis / N.V. Toroptsova, O.A. Nikitinskaya. - “Attending Physician” magazine, No. 03, 2009.
  7. Postmenopausal osteoporosis. Treatment and prevention of postmenopausal osteoporosis /S. V. Yureneva. - Consilium Medicum Volume 06/N 9, 2004.

Pathological destruction of bone tissue caused by systemic metabolic disorders due to hypoestrogenism. In half of the cases it occurs latently and is diagnosed after a fracture occurs. It can manifest itself as pain in the sacrum, lower back, interscapular region, pelvic bones, forearm and lower leg, curvature of the spine, and decreased height. Diagnosed using densitometry, determining the level of calcium, phosphorus, markers of bone resorption, calcitonin, parathyroid hormone. For treatment, hormonal agents, osteoresorption inhibitors, osteosynthesis stimulants, calcium and vitamin D preparations are used.

General information

Primary postmenopausal osteoporosis is the most common variant of osteoporetic disease, accounting for more than 85% of the structure of this metabolic disease of the musculoskeletal system. According to WHO, a densitometrically confirmed decrease in bone mineral density and a violation of their microarchitecture is observed in 30-33% of women over 50 years of age. In Russia, the frequency of forearm fractures typical of osteoporosis is more than 560 cases per 100 thousand postmenopausal patients, osteoporetic hip fractures - over 120 per 100 thousand. The social significance of the pathology is determined by its effect on disability and mortality in elderly women.

Causes

A decrease in bone mass and disruption of bone microarchitecture during postmenopause is associated with involutive processes occurring in the female body and age-related changes in lifestyle. Specialists in the field of gynecology have studied in detail the causes of the disorder and predisposing factors. Osteoporosis in older women is caused by:

• Decrease in estrogen levels. Female sex hormones are involved in the metabolism of calcium, an important structural component of bones that ensures their strength, renewal and restoration of bone tissue. Hypoestrogenism develops with insufficiency or decline of ovarian function, drug suppression of estrogen secretion, surgical removal of an organ in patients with tumors, endometriosis, or ectopic pregnancy.
• Poor nutrition. Calcium deficiency occurs with limited consumption of dairy products, fish, dietary meats, legumes, herbs, vegetables, fruits against the background of an excess of easily digestible carbohydrates, fats, coffee, and strong tea. Such a diet is characterized by a low content of calcium, substances that promote the absorption of the mineral by the body, and an increased concentration of inhibitors of its absorption in the intestine.
• Low physical activity. As a woman ages, her mobility decreases. The situation is aggravated by a decrease in the time of natural insolation, the presence of excess weight, diseases and pathological conditions that limit the ability to move independently - long-term bed rest in the treatment of chronic somatic pathology, the consequences of cerebrovascular accidents and heart attacks.

Risk factors for osteoporosis in the postmenopausal period are age exceeding 65 years, belonging to the Caucasian race, early menopause, underweight, a history of dyshormonal disorders, smoking, and alcohol abuse. The influence of heredity cannot be ruled out - the disease is more often detected in women whose close relatives suffered from osteoporosis or had frequent fractures. The likelihood of damage to the skeletal system also increases with more than three months of taking glucocorticoid drugs that affect calcium metabolism.

Pathogenesis

In postmenopausal osteoporosis, the balance between osteosynthesis and osteoresorption, the main mechanisms of bone tissue remodeling, is disrupted. Against the background of estrogen deficiency, the secretion of calcitonin, the thyroid hormone, which is a functional antagonist of parathyroid hormone, decreases, and the sensitivity of bone tissue to the resorptive effect of parathyroid hormone increases. The main effect of parathyroid hormone is an increase in the concentration of calcium in the blood due to increased transport through the intestinal wall, reabsorption from primary urine and osteoresorption. In parallel with this, osteoclasts are activated - cells that destroy bone tissue, insulin-like growth factors 1 and 2, osteoprotogerin, transforming β-factor, colony-stimulating factor and other cytokines that enhance bone resorption.

Additional elements of pathogenesis that contribute to the development of osteoporosis are deterioration in mineral absorption due to subatrophy of the intestinal epithelium and vitamin D deficiency, for sufficient secretion of which longer exposure to the sun is required. A decrease in physical activity in the postmenopausal period leads to a decrease in dynamic loads on the musculoskeletal system, which also slows down the processes of its remodeling. The situation is aggravated by deterioration of calcium absorption in the intestine and its increased excretion in the urine when taking glucocorticoids, often used in treatment regimens for endocrine, autoimmune, inflammatory and other diseases that affect elderly patients.

Symptoms of postmenopausal osteoporosis

In almost half of women, the disease is asymptomatic and is detected only after a fracture caused by a minor injury. In other cases, symptoms progress gradually. As bone mass is lost, the patient begins to feel pain in the lumbosacral region, which intensifies when lifting heavy objects, turning, or walking. Subsequently, a feeling of heaviness appears in the interscapular space, pain in the pelvic ring, and the long tubular bones of the lower leg. To get rid of pain and discomfort, additional rest in a lying position is required throughout the day.

The increase in the intensity of painful sensations leads to the fact that over time they bother the patient even at rest. Typically, poor posture and curvature of the spine are accompanied by kyphosis. Often, postmenopausal women with osteoporosis complain of weakness and fatigue during physical activity. The extreme forms of manifestation of the pathology are compression fractures of the lower thoracic and upper lumbar vertebrae with a decrease in their height, spontaneous or fractures of the ankles, bones of the forearm, and femoral neck that occur under minor loads. A characteristic sign is a decrease in height by several centimeters per year.

Complications

The most serious consequence of postmenopausal osteoporosis is disability due to curvature of the spine and frequent fractures of the limbs, aggravated by constant pain in the bones. It is difficult for the patient to move not only long distances, but also around the house, take care of herself, and perform simple everyday activities. A significant deterioration in the quality of life can provoke emotional disorders - anxiety, tearfulness, hypochondriasis, and a tendency to react depressively. Some women with osteoporosis experience long-term insomnia.

Diagnostics

If compression changes in the spine or typical fractures of the extremities are detected in a postmenopausal patient, it is first necessary to exclude osteoporosis. For diagnostic purposes, methods are used to assess the architecture of bone tissue and the degree of its saturation with calcium, as well as to detect biochemical markers of bone damage. The most informative are:

• Densitometry. Modern dual-energy X-ray osteodensitometers accurately determine how much bone density is reduced. With their help, it is easy to assess the mineralization of “marker” bones (forearm, hip joint, lumbar vertebrae) and the entire body. The method is applicable for diagnosing the early stages of postmenopausal osteoporosis. Instead of a classic dual-energy study, ultrasound screening of bone density (echodensitometry) and CT densitometry can be performed.
• Biochemical blood test. Laboratory tests determine the content of calcium, phosphorus and some specific markers that indicate impaired bone remodeling. With increasing age-related bone resorption, the level of alkaline phosphatase, osteocalcin in the blood, and deoxypyridonoline in the urine increases. When correlated with creatinine excretion, the determination of calcium in the urine is quite specific, the content of which increases with increased resorptive processes in bone tissue.
• Hormone analysis. Since postmenopausal osteoporosis is pathogenetically associated with age-related hormonal imbalance, a study of the level of thyrocalcitonin (TCT) and parathyrin is indicative for diagnosis. With involutive disorders of bone resorption, the concentration of calcitonin in the blood decreases, while the level of parathyroid hormone remains normal or reduced. A control study of the content of sex hormones confirms natural age-related hypoestrogenism.

Differential diagnosis is carried out with senile and secondary osteoporosis, malignant bone tumors and bone metastases, myeloma, fibrous dysplasia, Paget's disease, common traumatic fractures, scoliosis, spinal osteochondropathy, peripheral neuropathy. If necessary, the patient is consulted by an orthopedist, traumatologist, or endocrinologist.

Treatment of postmenopausal osteoporosis

The main goal of therapy is to prevent possible fractures by improving the mineralization and architecture of bones while simultaneously increasing the quality of life of patients. For this purpose, complex antiosteoporetic therapy is used, aimed at various parts of the pathogenesis of the disease. The standard treatment regimen for osteoporosis caused by postmenopausal changes in a woman’s body includes the following groups of drugs:

• Bone resorption inhibitors. Estrogens, their combinations with progestins or androgens, prevent premature bone destruction and are recommended if menopausal symptoms persist in the first years of postmenopause. If there are contraindications or the patient refuses to take sex hormones, they can be replaced with phytoestrogens, selective modulators of estrogenic activity or estrogen receptors. In addition to hormone replacement therapy, calcitonin, bisphosphonates, and strontium preparations have the effect of slowing down resorption.
• Bone formation stimulants. Osteogenesis is enhanced by the administration of parathyroid hormone, anabolic steroids, androgens, somatotropin, and fluorides. Accelerated bone remodeling with the use of these drugs is achieved by activating osteoblasts, enhancing anabolic processes, and stimulating hydroxylation. It should be taken into account that in case of postmenopausal disorders, the use of such drugs is limited by a number of contraindications and possible complications.
• Means of multifaceted action. Mineralization and architecture of bone tissue improves when taking calcium supplements, especially in combination with vitamin D, which allows such drugs to be classified as basic. The osseino-hydroxylate complex and flavone compounds also have a versatile effect on the processes of osteogenesis and bone destruction, which, with a minimal likelihood of complications, effectively inhibit the function of osteoclasts responsible for resorption and demineralization, stimulating osteoblastic osteopoiesis.

Effective treatment of osteoporosis in postmenopausal women is impossible without lifestyle and diet modifications. Elderly patients are recommended to exercise moderately, excluding falls, heavy lifting, and sudden movements. It is necessary to add foods rich in calcium to the diet - milk, cottage cheese, hard cheese, legumes, fish, and other seafood, giving up the abuse of coffee and alcoholic beverages.

Prognosis and prevention

Although postmenopausal osteoporosis is a progressive disease, regular maintenance treatment and a healthy lifestyle can significantly reduce the likelihood of fractures. For preventive purposes, postmenopausal women are recommended to take calcium supplements containing vitamin D, dosed insolation, diet correction, sufficient physical activity taking into account age norms, smoking cessation, limited consumption of products containing caffeine (coffee, tea, chocolate, cola, energy drinks) . If signs of osteoporosis are detected, corsets and hip protectors can become effective protection against loads that provoke fractures.

Osteoporosis (OP) develops gradually and is often clinically detected after fractures, which is the basis for calling it a “hidden epidemic.” According to WHO experts, AP today is one of the most common diseases: in Europe, the USA and Japan, 75 million people suffer from AP, and of all patients with AP, 80% are women. It is believed that one in three women over the age of 50 years has AP. In the Moscow population, the incidence of AP according to an epidemiological study among patients aged 50 years and older was 33.8%. 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, lead to an increase in the incidence of this disease. From the perspective of patient prognosis and public health prospects, femoral fractures due to AP are the most severe. The relative risk of death after such fractures is 6 times higher than in the general population of the corresponding age. Half of patients who survive a hip fracture never leave their home, and about 30% need outside help constantly. An assessment of the global trend showed that only due to the aging of the world population, the incidence of fractures, for example, of the femoral neck, in the period from 2005 to 2050. should double in size. In light of such a catastrophic increase in the incidence of fractures, the need for large-scale preventive measures is quite obvious as the main means that can counter this trend and somewhat slow down the increase in the incidence of AP.

Currently, there are two main types of AP: primary and secondary. Primary AP is the most common: the ratio of its frequency to the frequency of all forms of secondary AP reaches 4:1. Secondary AP can be divided into two large groups: AP caused by the underlying disease, for example, rheumatoid arthritis, and AP resulting from treatment (iatrogenic). In the first case, it is necessary to establish the underlying disease, the symptom of which is AP; in the second, the therapy that may have led to the development of AP should be analyzed.

Primary AP includes age-dependent bone loss and osteopathy of unknown etiology: juvenile (AP in children and adolescents), idiopathic (OP in young and middle-aged adults). However, the most common is primary AP, which is divided into postmenopausal and senile. Postmenopausal AP is associated with accelerated bone loss in women after the cessation of menstruation and is caused by estrogen deficiency. The most pronounced changes due to estrogen deficiency occur in trabecular bone. Activation of bone metabolism at the tissue level is characterized by an increase in the number of activated bone remodeling units; along with an increase in resorption, the formation of bone tissue also increases, but it cannot fully compensate for resorption, as a result of which the instability of bone trabecular architecture increases, which leads to an increased risk of developing trabecular bone fractures.

Senile AP is characterized by proportional loss of trabecular and cortical bone. 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. Histomorphometric studies showed a significant decrease in the number of osteoblasts in these patients, as well as a slowdown in remodeling processes (decreased osteoblastogenesis and osteoclastogenesis, decreased life expectancy of osteocytes).

Low bone mineral density (BMD) is not associated with specific clinical manifestations, and, as mentioned above, the main clinical symptom of AP is bone fractures that develop with minimal trauma, of which the most typical are fractures of the thoracic and lumbar vertebrae, the distal forearm and the proximal section of the femur. Vertebral fractures can be manifested by a decrease in height, an increase in thoracic kyphosis, a decrease in the distance between the costal arches and the iliac crests, and the appearance of a distance between the back of the head and the wall when measuring height. Back pain due to vertebral fractures does not have specific features, since it can be both acute (for example, with a compression fracture) and chronic (with gradual subsidence of the vertebral bodies under the weight of one’s own body). Vertebral fractures in combination with pain limit the ability of patients to carry out daily activities (dressing, cleaning, cooking, washing dishes); due to increased kyphosis, orthostatic stability is lost, which can increase the risk of falls.

Diagnosis of OP disease is centered around two parameters characterizing bone strength: BMD and bone quality. It should be noted that any clinical and instrumental methods for assessing the quality of bone tissue, other than BMD, are currently absent, therefore in clinical practice, to diagnose AP, they use the determination of bone mass, the equivalent of which is BMD, measured using X-ray densitometry (X-ray densitometry). ).

It is well known that based on an EBM examination in accordance with WHO criteria, a woman is diagnosed and subsequently given recommendations. If normal BMD indicators are detected - a T-score of more than -1 standard deviation - the patient is explained the importance of sufficient calcium intake from food, adequate physical activity and the negative effects of smoking and alcohol abuse. If the T-score is between -1 and -2 standard deviations below the average for a healthy young adult, then the need to add calcium and vitamin D supplements to preventive measures is indicated, and in the case of a T-score below -2.5 standard deviations, it is necessary to prescribe antiresorptive therapy.

It should be noted, however, that normal BMD measured using EBM does not always guarantee that the patient will not have a fracture, therefore, according to some experts, it is not advisable to examine all postmenopausal women using EBM. Today, risk factors (RFs) for AP have been well studied and are easy to determine in every woman. These risk factors include low body weight; previous fractures caused by minimal trauma; parental hip fractures; current smoking; long-term use of glucocorticoids orally; daily consumption of alcohol in the amount of three or more glasses of beer of 285 ml or three or more glasses of wine of 120 ml; rheumatoid arthritis and other causes of secondary AP. In this regard, the basis for identifying patients for whom therapy is indicated is the strategy of searching for individual cases, which consists in identifying individuals at high risk of fractures based on the assessment of risk factor, and the priority in diagnosis is not the fact of the presence of AP, but assessing the risk of developing a fracture.

The International Osteoporosis Foundation and WHO recommend that the risk of fragility fracture should be expressed as a short-term absolute risk, i.e. the probability of an event over a 10-year period. The 10-year period was chosen because it covers the expected duration of treatment and includes the development of beneficial effects that continue after cessation of therapy.

An algorithm for identifying individual cases of high risk of fractures was developed in the UK by an expert group of specialists led by J. Kanis, taking into account the interaction of clinical risk factors for fractures, age and the presence or absence of data on BMD. Using the FRAXTM tool (http://www.shef.ac.uk/FRAX), the 10-year probability of hip fracture and other common AP-related fractures (vertebrae, radius and humerus) can be calculated in older adults from 40 to 90 years.

In this regard, new approaches to the diagnosis of AP, based on determining the absolute risk of fractures, expressed in the probability of developing a fracture over the next 10 years of life, make it possible to begin treatment in patients with previous fractures with minimal trauma and in patients aged 65 years and older with the presence of other FRs without taking into account the IPC. In patients under 65 years of age, therapeutic tactics are determined based on a combination of risk factors and densitometry results.

Treatment of AP includes both non-drug therapy (giving up bad habits, physical exercise, fall prevention) and pharmacological intervention. The main goal of therapeutic intervention in postmenopausal AP is to normalize the process of bone remodeling, which leads to stabilization or increase in BMD, improved bone quality and reduced incidence of fractures with a corresponding reduction in the necessary costs for patients and health authorities.

Pathogenetic therapy of AP includes drugs that slow down bone resorption: bisphosphonates (BP), calcitonins, selective modulators of estrogen receptors, estrogens, as well as drugs that primarily enhance bone formation (parathyroid hormone), and medications with multifaceted action (vitamin D and its active metabolites), double actions - increase bone formation and reduce bone destruction (strontium ranelate).

The first-line drugs in the treatment of AP are BF. They suppress increased bone resorption in postmenopause by physicochemical binding to hydroxyapatite on the resorptive surface and a direct effect on osteoclasts, leading to disruption of their metabolism and functional activity, induction of their apoptosis, which contributes to a shift in the balance towards bone formation. Among the BPs for the treatment of postmenopausal AP, ibandronic acid (Bonviva) is used in clinical practice - a drug that, when taken 1 tablet at a dose of 150 mg once a month or at a dose of 3 mg IV once every 3 months, leads to normalization of bone metabolism and increasing BMD, reducing the risk of fractures. The efficacy and tolerability of daily oral Bonviva, including extended dosing interval regimens, and IV administration in postmenopausal AP have been evaluated in numerous randomized clinical trials (RCTs).

A randomized, double-blind, multicenter (73-center) clinical trial (BONE) of 2,946 postmenopausal women with one to four vertebral fractures and lumbar spine BMD less than -2.0 SD T-score demonstrated the effectiveness of daily ibandronate. 2.5 mg and intermittent dosing of 20 mg every other day for the first 24 days every 3 months in relation to a reduction in the risk of vertebral fractures after 3 years of treatment by 62% and 50%, respectively (p< 0,001 в сравнении с плацебо) на фоне приема 500 мг кальция/сут и 400 МЕ/сут витамина D. Данные ретроспективного анализа продемонстрировали, что ежедневный прием снижал риск внепозвоночных переломов на 69% (p = 0,012) в группе высокого риска (с МПК шейки бедра < -3,0 SD по Т-критерию). Кроме того, показана хорошая переносимость перорального ибандроната . Изучение биопсийного материала подвздошной кости, проведенное в рамках исследования BONE, показало отсутствие негативного влияния препарата на минерализацию костной ткани .

To optimize patient adherence, two RCTs were conducted using the more convenient once-monthly dosing regimen of ibandronate. The MOPS (Monthly Oral Pilot Study) multicenter (5 sites), double-blind, placebo-controlled RCT examined the effect of different doses (50 mg, 100 mg, and 150 mg) of ibandronate given once a month on bone resorption in 144 healthy women. in postmenopause. At the indicated doses, the drug effectively suppressed bone resorption, which was confirmed, in particular, by a reliable and significant decrease in the levels of bone turnover markers (serum CTX and urine CTX), while in the groups receiving 100 mg and 150 mg, serum CTX decreased by 40 .7% and 56.7%, and urine CTX by 34.6% and 54.1%, respectively (p< 0,001 по сравнению с плацебо) . По причине небольшого числа участниц исследования и отсутствия приема ими препаратов кальция и витамина D возникла необходимость в дальнейшей оценке перорального приема ибандроната 1 раз в месяц, в связи с чем было инициировано исследование MOBILE (the Monthly Oral iBandronate in Ladies).

MOBILE was a multicenter (65 sites, 1609 patients), double-blind, parallel-group, phase III RCT designed to compare the efficacy and safety equivalence of once-monthly oral ibandronate with 2.5 mg daily dosing. After 1 year, the average BMD in the lumbar spine increased by 4.3% when taking the drug 50 mg orally 2 days in a row once a month, by 4.1% when taking 100 mg once a month, by 4.9% in regimen - 150 mg 1 time/month and by 3.9% when taking 2.5 mg daily. ANOVA analysis of variance allowed us to prove a significantly higher effectiveness of the 150 mg regimen once a month compared to daily dosing. A significant increase in spine BMD, observed after 1 year with all regimens of taking ibandronate once a month, was confirmed after two years of the study: by 5.3%, 5.6% and 6.6% when taking 50/50 mg, 100 mg and 150 mg, respectively, and by 5.0% with a daily dose of 2.5 mg. In addition, there was an increase in BMD in the proximal femur in all treatment groups after 1 year of therapy. After 2 years, the increase in BMD at a dose of 150 mg monthly was significantly higher than with a daily dose of 2.5 mg (p< 0,05) . При всех режимах приема один раз в месяц были получены результаты не хуже, чем при ежедневном приеме; однако статистический анализ продемонстрировал преимущество дозы 150 мг, принимаемой один раз в месяц.

Study results consistently confirmed that oral administration was not associated with an increased risk of side effects and had a safety profile equivalent to that of placebo. In two RCTs, daily and intermittent use of ibandronate in older adults did not increase the risk of adverse events and did not affect aortic calcification. The relatively large doses required for once-monthly dosing did not have a significant effect on overall ibandronate tolerability.

A 48-week, multicenter, open-label, parallel-group RCT assessed the effectiveness of oral ibandronate (2.5 mg/day) depending on the duration of the drug-breakfast interval (30 or 60 minutes). At the 30-minute interval, there was a smaller increase in BMD in the lumbar spine and proximal femur compared to baseline values, as well as a less pronounced decrease in bone turnover markers than at the 60-minute interval.

A 12-month, multicenter (65 centers), double-blind, double-masked, parallel-group RCT (MOTION) showed comparability of the results of BMD dynamics in the lumbar spine and proximal femur with weekly intake of 70 mg of alendronate and monthly intake of 150 mg of ibandronate after a year of therapy. Thus, the increase in spine BMD was 5.1% and 5.78%, and in the overall hip index 2.94% and 3.03% for ibandronate and alendronate, respectively. Thus, less frequent use of ibandronate did not affect the effectiveness of antiresorptive treatment.

The use of ibandronate for the treatment of postmenopausal AP by intravenous injection has been investigated in several programs. The most recent of these was the 2-year DIVA study, which demonstrated comparable effects of ibandronate on BMD and bone markers across different routes of administration—2 mg intravenously every 2 months or 3 mg every 3 months compared with daily 2.5 mg orally. It is important to note that the annual cumulative dose (ACD) for intravenous administration was 12 mg per year, and for oral administration was approximately 5.5 mg/year, which is associated with low absorption of the drug in the gastrointestinal tract, which is approximately 0.6 % of the dose taken orally. All patients received an additional 500 mg of calcium and 400 IU of vitamin D. After 2 years of treatment, in the group receiving 3 mg of ibandronate intravenously, the increase in spine BMD was 6.3% compared to 4.8% with daily dosing of 2.5 mg ( R< 0,05). Обе внутривенные дозы препарата показали больший прирост МПК по сравнению с исходными данными, в том числе в области проксимального отдела бедра по сравнению с ежедневным приемом.

Tolerability of intravenous ibandronate was comparable to daily oral ibandronate, with study drug-related adverse events occurring at similar rates of 39.0% and 33.3%, respectively. It should be noted that with intravenous administration, influenza-like syndrome was more common (4.9%). It was mainly associated with the first administration of the drug, occurred within the first 24 hours after intravenous injection, had a mild or moderate intensity and resolved independently or after taking antipyretic drugs after 1-2 days without any serious consequences for the patient. Adverse events related to kidney damage were rare (in less than 3% of women in each group), and the decrease in creatinine clearance was approximately the same in patients of all three groups (14-17%).

The effects of different doses and dosing regimens of ibandronate on fracture risk were not specifically examined in the studies described above. All studies recorded clinical fractures with radiographic confirmation as an adverse event. For this reason, two meta-analyses of studies were conducted to evaluate the effect of ibandronate on the incidence of nonvertebral fractures, determining the dependence of the effect on the annual cumulative dose of the drug. In a meta-analysis, Cranney A. et al. High-dose ibandronate (150 mg once a month for 2 years and 3 mg intravenously every 3 months) reduced the risk of nonvertebral fractures by 38% compared with 2.5 mg daily. The effectiveness of high doses was confirmed in a meta-analysis published in 2008 by Harris S. T. et al., which showed that the use of these regimens for two years compared with placebo significantly reduced the risk of six major fractures (clavicle, humerus, forearm, pelvis, hip and tibia) by 34.4% (p = 0.032), all non-vertebral fractures by 29.9% (p = 0.041) and clinical fractures by 28.8% (p = 0.010). High-dose ibandronate prolonged time to six major fractures (p = 0.031), all nonvertebral fractures (p = 0.025), and clinical fractures (p = 0.002) compared with placebo.

In everyday clinical practice, the therapeutic benefits of oral bisphosphonate therapy are often offset by the fact that the patient does not follow the doctor's orders and does not take prescribed medications. At the same time, strict adherence to the doctor’s prescriptions is the main factor determining the effectiveness of the treatment. Therapy for chronic diseases, which includes postmenopausal AP, is characterized by a low level of compliance with doctor’s prescriptions. Consequently, less frequent dosing of the drug orally, which reduces the irritating effect of bisphosphonates on the mucous membrane of the esophagus and helps reduce the incidence of side effects from the gastrointestinal tract, provides greater convenience during long-term therapy. In addition, in the presence of contraindications for taking bisphosphonates orally, as well as the inability to remain in an upright position for an hour or in the case of taking a large number of tablets for the treatment of comorbid conditions, patients with postmenopausal AP have the opportunity to receive long-term antiresorptive therapy by intravenous administration of a drug with proven effect on reducing the risk of fractures.

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N. V. Toroptsova, Doctor of Medical Sciences
O. A. Nikitinskaya, Candidate of Medical Sciences
IR RAMS, Moscow