Osteoporosis: causes, diagnosis and treatment

Osteoporosis

(some call it “bone osteoporosis,” which is incorrect, since the word already contains the root “osteo,” which means “bone”) is a disease that is systemic and progressive, the main symptom of which is a decrease in density and disruption of the structure of bone tissue. Decreased bone density leads to an increased likelihood of developing fractures. A characteristic feature of osteoporotic fractures is their occurrence due to minor loads. It is the ease of fractures that is the main danger in osteoporosis, since extremely important bone structures of the human body - the spine, the femoral neck - can be susceptible to fractures. Fractures lead to immobility of the patient, which in old age is fraught with a significant number of complications - from the appearance of bedsores to the development of congestive pneumonia, which can be life-threatening. Few people know, but osteoporosis is now the fourth leading cause of death in people - it is second only to cardiovascular diseases, tumors and diabetes. And the main cause of death in patients with this diagnosis is a fracture of the femoral neck.

Causes of osteoporosis

postmenopausal osteoporosis
in women (associated with low production of female sex hormones after menopause; the vast majority of women over 60 years of age describe its symptoms);
senile osteoporosis
is a broader concept than menopausal osteoporosis. The aging of the human body is accompanied by disruption of the internal structure of a significant number of organs, including bone tissue. It is the general aging of a person that causes a decrease in bone strength in old age;
glucocorticoid osteoporosis
develops in patients receiving long-term treatment with glucocorticoids - hormones of the adrenal cortex and their synthetic analogues, one of the side effects of which is disruption of the functioning of bone tissue;
secondary
is called
osteoporosis,
the cause of which is any chronic serious disease; Moreover, osteoporosis is one of the symptoms or complications of a primary disease - that is why it is called secondary, it seems to develop second. The cause of secondary osteoporosis can be diseases such as diabetes mellitus, malignant tumors, chronic kidney disease with the development of renal failure, some lung diseases, thyrotoxicosis (excessive thyroid function), hypothyroidism (reduced thyroid function), chronic hepatitis, parathyroid adenoma ( primary hyperparathyroidism). Also, the cause of its development may be a long-term deficiency of calcium and vitamin D in food - this disrupts the flow of calcium into the blood, and therefore the body’s needs for calcium are met at the expense of reserves in the bones. The result is osteoporosis.

Osteoporosis - what kind of disease is it?

It is customary to distinguish between primary and secondary osteoporosis. The first occurs in 80-85% of cases, the second accounts for no more than 15-20%. The primary form of osteoporosis is divided into 4 types:

In postmenopausal osteoporosis, bone mass rapidly decreases with primary damage to the trabecular bone. During the illness, fractures of the bones of the distal forearm often occur.
In senile osteoporosis, age-related loss of bone mass occurs. The skeleton suffers from increased fragility in the spine, hips, and forearms.
In juvenile osteoporosis, the disease affects the bones of young people aged 8-14 years.
With idiopathic osteoporosis, the skeleton becomes fragile and susceptible to fractures.

The likelihood of developing secondary osteoporosis increases with the following diseases: genetic pathologies, renal hypercalciuria, Gaucher disease, muscovic fibrosis and other disorders.

Mechanism of development of osteoporosis

In bone tissue, two mutually opposite processes constantly coexist - osteogenesis (formation of bone tissue) and resorption (destruction) of bone tissue. Bone is a living structure that provides important support and organization functions to the human body. The human bone is a complex network of interconnected and intersecting bone beams, the direction of movement and strength of which make it possible to counteract the mechanical loads acting on the bone as a whole (the weight of the bone and muscles, the weight of internal organs and external loads, loads due to body position or acting on external acceleration, etc.). The nature of loads changes throughout a person’s life - body weight changes, height often changes with age, the nature of activity changes - all this forces the bone to adapt to new conditions and remain resistant to the forces acting on it. Bone beams are destroyed in one place and formed in another - this process is called bone remodeling and occurs constantly.

Special cells, osteoclasts, are responsible for the destruction of bone tissue during remodeling, which, like bulldozers, “bite” into bone tissue and destroy it. The formation of new bone beams is carried out by “mason” cells, osteoblasts, which form new bone tissue - the bone matrix, into which calcium salts are deposited, ensuring the strength of the constructed structure.

Increased bone resorption processes combined with weakened bone formation processes are the main cause of the development of osteoporosis. Osteoporosis occurs when old bone tissue is destroyed and new bone tissue is formed in insufficient quantities. Also, the reason for its appearance may be insufficient intake of calcium salts into the bones - in this case, the bone becomes soft and ceases to perform frame and supporting functions.

It should be remembered that the causes of osteoporosis are always directed against the formation of new bone, or “help” the destruction of bone tissue - both of which ultimately lead to fractures.

Postmenopausal period

In the postmenopausal period, correction of osteoporosis is a complex work in two directions.

Classical measures for the treatment of postmenopausal osteoporosis. In this case, it is necessary to take calcium-containing medications and drugs in combination with vitamin D3, physiotherapy and treatment of concomitant diseases.
Hormone replacement therapy that corrects the deficiency of the female hormone estrogen.

Sources:

Internet resources

https://etospina.ru

https://www.f-med.ru

https://www.diagnos.ru

Risk factors for osteoporosis

In childhood and adolescence, the process of bone tissue formation significantly prevails over its resorption. The older a person gets, the more bone destruction begins to prevail over its formation. The process of bone resorption intensifies especially in women after menopause. That is why osteoporosis in women is a typical and very common disease that occurs in old age.

There are factors that increase the risk of developing osteoporosis:

female gender (women are much more susceptible to this disease than men);
osteoporosis in blood relatives in the family (genetic predisposition to this disease is very important);
age (as we mentioned earlier, with age the likelihood of developing the disease increases significantly);
low mobility (immobilization, fixation of the patient’s limbs or body in case of injury, significant patient weight, mental disorders that make movement difficult - all these conditions are causes of the development of osteoporosis);
drug therapy using glucocorticoids, high doses of thyroxine (a synthetic analogue of the thyroid hormone); bone tissue is also negatively affected by long-term use of aluminum-containing drugs - for example, antacids used to reduce the acidity of gastric juice during gastritis or peptic ulcers;
the patient is overweight or underweight.

The patient cannot always change anything about the causes of osteoporosis, even if he understands that they can be dangerous. Indeed, neither gender nor age (the main risk factors) can be changed. However, there are factors that the patient can and should change in order to reduce the risk of developing such a dangerous disease. Smoking, excess consumption of alcohol and caffeine-containing drinks, lack of exercise, low consumption of foods rich in calcium (for example, dairy), little sun exposure, insufficient vitamin D intake - all of these factors can be changed, which is why they are called modifiable factors. risk.

Osteoporosis - symptoms and signs

Unfortunately, osteoporosis is a hidden disease that occurs for a long time without noticeable symptoms, and therefore its diagnosis is often delayed. Very often, the first symptom is a fracture - only after the fracture does the patient begin the examination and learn that the cause of the injury was osteoporosis.

At the same time, there are symptoms that make it possible to notice this disease at an earlier stage, before fractures appear. Patients are often concerned about changes in posture, stooping, decreased height, and accelerated destruction of dental tissue. Bone pain is one of the important signs to suspect the development of osteoporosis. Most often, pain occurs in the spine, hip bones, bones of the forearms and wrist. Often the pain intensifies with prolonged exposure to an uncomfortable position or mechanical stress. When there is a fracture or a sharp decrease in the height of the vertebrae, the pain is localized in the back, between the shoulder blades, and in the lumbar region. A symptom of calcium deficiency in the blood may be the appearance of convulsive muscle contractions.

Severity

There are several degrees of osteoporosis. They characterize the severity of the disease;

Grade 1. Initial stage, at which there may be no clinical symptoms. Changes in bones can be detected during a random diagnosis for another disease. In some cases, brittle hair and nails and dry skin may occur.
Degree 2. Destructive changes are isolated in nature. Changes are detected in one part of the skeleton. Most often this is the thoracic spine or lower extremities. Clinically, stage 2 osteoporosis is expressed in pain localized in the affected area. There may be convulsions and rapid heartbeat.
Grade 3: Major changes are found in the bones. The bones become flattened, and when the spine is affected, a decrease in the height of the vertebrae is observed. In this regard, the patient's height decreases. Patients complain of severe pain and a hump forms on the back.
Grade 4. The most severe stage of osteoporosis. Radiologically it is expressed in pronounced structural changes in the bones. The patient's height may decrease by up to 10 cm. Fractures occur due to minor injuries.

Diagnosis of osteoporosis

Currently, diagnosing osteoporosis does not present significant difficulties. We only need to remember that traditional radiography is not able to assess the degree of development of osteoporosis, so other methods are used for diagnosis. Radiography allows one to only suspect the presence of osteoporosis based on a characteristic change in bone density on X-ray images, however, to plan treatment and assess the dynamics of changes in bone density, it is necessary to have quantitative information about the condition of the bone - i.e. it is necessary to be able to express bone density digitally.

Quantitative assessment of bone density is central to the diagnosis of osteoporosis. For this study, a special term was invented - “densitometry”,

those. density measurement. It is often written differently – “osteodensitometry”, emphasizing that bone density is measured.

Densitometry can be of three main types:

X-ray densitometry (synonyms: DEXA, dual-energy X-ray computer densitometry);
computed tomographic densitometry;
ultrasonic densitometry.

With X-ray densitometry

X-rays of bones are taken at standard points (usually there are three standard points: femoral neck, lumbar spine, radius). After receiving the X-ray image, a special computer program calculates the bone density in the area of interest to the doctor and compares it with indicators characteristic of a healthy person of the same age (this is called the Z-index) or for a healthy person aged 40 years (this indicator is called the T-index ).

Diagnosis of osteoporosis

is carried out according to the deviation of the T-index from normal values:

from 0 to -1 – normal bone density;
from -1 to -2.5 – osteopenia (loss of bone tissue);
less than -2.5 – osteoporosis.

With computed tomographic densitometry

Computed tomography is performed on a multislice tomograph, followed by calculation of bone density and comparison with the reference one. As a result, the density of 1 cubic centimeter of bone tissue in the study area is calculated, and the T- and Z-indices are calculated. The advantage of computed tomographic densitometry is its high accuracy and the ability to calculate bone tissue density regardless of the patient’s weight, the presence of adhesions, and metal structures, which can make it difficult to obtain results with conventional X-ray densitometry. The disadvantage of densitometry on a tomograph is the increased radiation exposure to the patient’s body.

Ultrasound densitometry

carried out by measuring the speed of passage of an ultrasonic wave through bone tissue. It has been proven that a decrease in bone density makes it looser and does not allow the bone to quickly conduct sound waves. The lower the bone density, the slower the sound wave travels along the surface of the bone. The ultrasound densitometer is equipped with special sensors for measuring the speed of ultrasound along the surface of the bones, and the built-in software of the device allows you to calculate bone density with the determination of T- and Z-indexes.

Ultrasound densitometry uses superficially located bones to determine density - the phalanges of the fingers, the radius on the forearm, the anterior surface of the tibia, the fifth metatarsal bone on the foot. The indicators calculated using ultrasound densitometry (T- and Z-indices) can be compared with similar indicators obtained from X-ray densitometry (that is, if osteoporosis was detected during X-ray densitometry, then ultrasound densitometry will reveal the same changes). At the same time, if the patient underwent X-ray densitometry during the first study, which revealed osteoporosis, and then treatment for osteoporosis was prescribed, then the second study should be carried out using the same assessment method, that is, also X-ray densitometry - only in this case will it be most reliable evaluate the effectiveness of treatment. Of course, the same rule applies to ultrasound densitometry - if treatment is carried out based on the results of the initial ultrasound examination, then monitoring of the treatment results should be carried out using ultrasound densitometry.

Diagnosis of osteoporosis using ultrasound densitometry has a number of advantages - ultrasound densitometry is not accompanied by radiation and can be carried out in a convenient environment for the patient for a fairly short time. The safety of the study is so high that ultrasound densitometry can be performed on both children and pregnant women.

In short, densitometry allows you to completely solve the problem of diagnosing osteoporosis, while any densitometry method is cheap, painless, and accurate.

Densitometry should be performed on all women aged 65 years

– following this simple rule could significantly reduce the incidence of fractures among older women. At the same time, densitometry is absolutely indicated for other groups of patients, including young patients. Among the indications for densitometry, the following should be noted:

early onset of menopause;
hormonal disorders in women, accompanied by estrogen deficiency, with the development of amenorrhea (absence of menstruation);
low body weight (including due to a disease such as anorexia nervosa);
presence of blood relatives suffering from osteoporosis;
the presence of primary hyperparathyroidism (parathyroid adenoma);
the presence of secondary hyperparathyroidism due to chronic renal failure;
thyrotoxicosis (due to diseases such as diffuse toxic goiter, polynodose toxic goiter, toxic thyroid adenoma);
decreased testosterone levels in men;
long-term immobilization for fractures or other injuries;
Itsenko-Cushing syndrome and disease;
long-term use of glucocorticoids;
the presence of rheumatic diseases (spondyloarthritis, rheumatoid arthritis), which are often combined with the development of osteoporosis.

It is important to understand that osteoporosis significantly complicates the treatment of joint diseases. Osteoporosis of the joints reduces the strength of the bones that articulate at the joint. Nowadays, endoprosthetics of hip and knee joints for arthrosis has become widespread. In this case, instead of a joint, the patient is fitted with a metal endoprosthesis, which is attached to the bones that form the joint. The stability of the resulting structure directly depends on the strength of the bones that bear the load of the endoprosthesis. The presence of osteoporosis of the joint creates preconditions for instability of the endoprosthesis, bone fractures in the area where the endoprosthesis is attached, and the development of severe complications. Therefore, diagnostics aimed at identifying osteoporosis is mandatory for all patients planning to undergo endoprosthetics.

Laboratory tests are of auxiliary importance in the diagnosis of osteoporosis. There are a number of markers (they are also called “osteoporosis tests”

), allowing to assess the severity of osteoporosis and the dynamics of its progression (osteocalcin, bone fraction of alkaline phosphatase, B-crosslaps, pyridinoline, etc.), however, their diagnostic significance is lower than the significance of densitometry.

When examining a patient with a suspected disorder of bone tissue density, important laboratory indicators are also mandatory:

ionized calcium, parathyroid hormone, 25-hydroxyvitamin D;
TSH, T4 St. (thyroid hormones);
for women – sex hormones (estradiol, testosterone, etc.);
for men – the level of free testosterone in the blood.

Degrees of development of the disease and their diagnosis

The degree of development of osteoporosis is determined either during the diagnosis process or by clinical manifestations.

The main diagnostic method that allows you to identify osteoporosis in the early (asymptomatic) stages is densitometry, or dual-energy X-ray absorptiometry - a special study that determines bone mineral density (BMD). Using these tests, a diagnosis of osteoporosis can be made with a loss of only 3-5% of bone mass8.

Indications for densitometry in older people:

women over 65 years of age and men over 70 years of age;
patients with concomitant diseases that require taking medications that reduce bone density (glucocorticoids, antacids, immunosuppressants);
patients with previous fractures;
evaluation of osteoporosis treatment results9.

Traditional radiography is also used, but it is capable of recording signs of osteoporosis with the loss of only 20-35% of bone tissue.

Treatment of osteoporosis

Currently, we can confidently say that the treatment of osteoporosis

should be carried out in specialized centers with significant experience in managing patients with this pathology. Osteoporosis is a complex multifactorial problem, the development of which is caused by endocrine, age-related, and behavioral factors; therefore, doctors of several specialties (endocrinologist, rheumatologist, cardiologist, neurologist) often take part in the treatment of osteoporosis. At the same time, one doctor must be in charge, must be the “conductor” of this orchestra, must know how to treat osteoporosis and determine examination tactics, as well as decide which specialists should be involved in consultations if necessary. Most often, this doctor is an endocrinologist - it is endocrinologists who most often treat osteoporosis these days.

The North-Western Center for Endocrinology, as a specialized endocrinology center, provides comprehensive diagnosis and treatment of osteoporosis in St. Petersburg, Vyborg and other cities of the Leningrad region. The center's endocrinologists independently perform ultrasound densitometry on patients, which allows them to quickly establish a diagnosis and determine how to treat osteoporosis, as well as objectively evaluate the results of the therapy.

The main goals in the treatment of osteoporosis are increasing bone mass (by increasing the deposition of new bone tissue and reducing the destruction of existing bone tissue), preventing the development of fractures, reducing or completely eliminating pain, and ensuring optimal motor mode for patients.

Treatment of osteoporosis consists of several important and interconnected stages:

First of all, the main diseases that cause osteoporosis are treated (thyrotoxicosis, hypothyroidism, Itsenko-Cushing syndrome and disease, hypogonadism, etc.);
therapy aimed at increasing bone mass (calcium preparations, vitamin D, drugs from the bisphosphonate group - Fosamax, Forosa, Fosavance, Zometa, Aklasta, Bonviva, etc.);
drugs aimed at reducing the intensity of pain.

In this article, we will not dwell in detail on therapy aimed at treating the underlying disease, if any, as this will take too much time. Let's discuss the modern concept of treating osteoporosis, aimed at increasing bone mass.

Currently, combination treatment of osteoporosis using:

vitamin D preparations (aquadetrim, vigantol), or activated forms of vitamin D (alfacalcidol, alpha D3-Teva, etalfa);
calcium preparations (containing calcium carbonate or calcium citrate);
drugs from the bisphosphonate group.

If the first two groups of drugs (vitamin D and calcium) are aimed at increasing the formation of bone tissue by increasing the supply of calcium to the patient’s body, then the second group (bisphosphonates) is aimed at suppressing bone resorption (bone breakdown). The main effect of bisphosphonates is to block the work of osteoclasts, the cells responsible for the destruction of bone tissue. Currently, even very long-term, up to 10 years, use of bisphosphonates is considered safe. The cheapest and most studied drug from this group is sodium alendronate (Fosamax, Forosa), which is taken once a week. Other drugs that appeared later allow you to take them once a month, or once every few months. Bisphosphonates for osteoporosis are the main “strike force” of doctors, due to their effectiveness and safety.

Correctly selected treatment for osteoporosis allows you to increase bone density by 5-10% per year, which greatly reduces the risk of developing fractures. It should only be recalled that this therapy is long-term, designed to last for years of use. You should not think that treatment for one or two months will give any noticeable result.

Postmenopausal osteoporosis: calcium supplements in modern prevention and treatment strategies

Osteoporosis (OP) is a metabolic disease of the skeleton, characterized by a decrease in bone mass, disruption of the microarchitecture of bone tissue and, as a consequence, fractures with minimal trauma. Fractures mainly occur in the vertebral bodies, femoral neck, proximal humerus, or other locations. Most patients suffering from AP are postmenopausal women. Currently, AP is one of the main causes of disability, decreased quality of life and premature mortality in older people, becoming a global problem. In the United States, AP is among the epidemic diseases, affecting more than 20 million people. In our country, this disease affects more than 30% of women aged 50 years (1 case in 3 women), while on average 24% of them suffered at least 1 fracture [1]. Mortality due to complications caused by osteoporotic fractures in the population of Caucasian women over 50 years of age is 2.8%, which corresponds to the mortality rate from breast cancer (BC). Moreover, the risk of hip fracture is equal to the total risk of breast cancer, uterine cancer and ovarian cancer [2].

Etiology

There are two main types of AP: primary (postmenopausal and senile) and secondary, which develops as a consequence of another pathological process (for example, with long-term use of glucocorticoids, etc.). In the pathogenesis of postmenopausal AP, estrogen deficiency and the associated accelerated loss of bone mass become of primary importance, so women are 2 times more likely than men to suffer from AP. The main reasons for the development of senile AP are a decrease in calcium intake, impaired absorption in the intestine and vitamin D deficiency, which results in secondary hyperparathyroidism and accelerated bone remodeling. Postmenopausal AP is the result of age-related estrogen deficiency. In the first 15 years of menopause, up to 75% or more bone loss can occur. The metabolically active trabecular bone of the vertebral bodies responds most quickly to estrogen deficiency, which begins to decrease significantly even in perimenopause. Bone loss from the radius begins in the second year after menopause. The lower the estrogen level, the faster bone loss occurs. Women with low premenopausal bone mass and accelerated bone loss at menopause have the highest risk of fractures. Bone loss in women aged 50 to 64 years can be up to 22%. Women who take drugs that block the synthesis of estrogen in the ovaries, as well as those who have undergone oophorectomy, are also at risk. In the latter, bone loss doubles.

Pathogenetic mechanisms of bone loss

In the pathogenesis of postmenopausal AP, the leading factor is a deficiency of sex hormones, which leads to an acceleration of bone metabolism processes with an imbalance in the direction of bone resorption [3, 4]. Sex hormones affect bone tissue by binding to specific receptors on osteoblasts, and spongy bone tissue is a specific 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), alpha 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. [5]. The discovery of the RANK/RANKL/OPG cytokine system played an important role in understanding the pathogenesis of AP. RANK (Receptor Activator of Nuclear Factor kappa B) is secreted by osteoclasts and their precursor particles and activated by RANKL (Receptor Activator of Nuclear Factor kappa B Ligand). RANKL is a signaling protein produced by osteoblasts. By binding to RANK, it causes differentiation and activation of osteoclasts. The endogenous inhibitor of RANKL is OPG. It regulates the balance of bone remodeling [6]. A change in the RANKL/OPG ratio towards the former leads to resorption and loss of bone tissue and, as a consequence, the development of bone diseases. Before menopause, the processes of bone resorption and formation are balanced. Decreased estrogen levels during menopause or after oophorectomy lead to increased production of RANKL, which is a major mediator of osteoclast formation, function, and survival. As a result, bone resorption increases. Excessive resorption causes bone loss, or more precisely, the development of AP. Therefore, RANKL inhibition improves bone health in AP. The pathogenesis of AP is also associated with disruption of the structure of the collagen network.
Collagen fibrils are the mechanical basis of all types of connective tissue, in particular bone. Type I collagen forms the most important component of the collagen network - extended fibrils, which are mineralized by calcium hydroxyapatite and bind calcium ions with amino acid residues. The interaction of calcium and collagen depends on the activity of a number of cofactors (Ca2+, Mg2+, Fe2+, Mn2+, Zn2+, Cu, etc. ions) and enzymes that regulate the level of intracellular calcium. Collagen biosynthesis is influenced by Ca-dependent proteins.

Basic principles of prevention and treatment

AP is a chronic disease that requires long-term treatment. The main goal of its treatment is to normalize the processes of bone remodeling, i.e. suppression of bone resorption and stimulation of bone formation, which leads to improved bone quality and a reduction in the incidence of fractures. Bone turnover is characterized by coupling, and with a decrease in bone destruction, bone formation also decreases, and with an increase in bone formation, bone resorption gradually increases. This is achieved through the use of non-drug (preventive) and pharmacological methods (pathogenetic therapy). Pathogenetic therapy of AP includes antiresistent drugs that suppress bone resorption, act on the osteoclast (bisphosphonates, denosumab, selective estrogen receptor modulators, estrogens), enhance bone formation (fluorides, anabolic steroids, androgens), as well as drugs that have a multifaceted effect on bone tissue ( calcium salts, vitamin D and its active metabolites, etc.) [7, 8]. Currently, the most widely used first-line drugs for the treatment of postmenopausal AP are denosumab and nitrogen-containing bisphosphonates. The mechanisms of action of denosumab and bisphosphonates differ significantly. Bisphosphonates
(BPs) – alendronic acid, risendronic acid, ibandronic acid, zoledronic acid.
BPs are incorporated into the bone matrix at the site of resorption and influence the functioning of activated osteoclasts, affecting mainly trabecular bone tissue. BFs are analogs of inorganic pyrophosphates in which the oxygen atom is replaced by a carbon atom, which makes the molecule more stable. During bone resorption, the osteoclast takes up BP, most likely together with calcium and bone matrix [9]. As a result, the modification of signaling proteins important for normal osteoclast function stops. Thus, the functioning of the osteoclast deteriorates, the resorptive surface decreases, which can subsequently lead to apoptosis [10, 11]. Recommended for increasing bone mineral density (BMD) in patients with postmenopausal AP. Denosumab
.
Monoclonal human antibody to receptor nuclear factor kappa beta ligand (RANKL) [12]. It is known that the basis for the development of AP is the excessive production of RANKL by osteoblasts. By binding to RANKL like OPG (osteoprotegerin), denosumab prevents RANK from interacting with RANKL and reduces the recruitment of mature osteoclasts. As a result, differentiation, activity and viability of osteoclasts decrease, and, as a result, bone resorption is suppressed and BMD increases in all parts of the skeleton. Unlike other antiresorptive drugs, denosumab reduces the formation of osteoclasts rather than impairs the function of mature cells. In addition, being a biological drug, denosumab does not accumulate in bone tissue and does not have a delayed effect with a complete reversal of the effect after treatment is discontinued [13, 14]. Progressive trabecular and cortical bone loss has been shown to be associated with an increased incidence of vertebral and hip fractures. By suppressing biochemical markers of bone turnover and increasing BMD - trabecular and cortical, denosumab effectively prevents fractures in patients with postmenopausal AP, prevents the loss of BMD and promotes its increase. Denosumab may contribute to the development of hypocalcemia, so it is important to compensate for vitamin D deficiency before starting treatment and ensure adequate calcium intake. New clinical guidelines from the American College of Physicians (ACP) for the treatment of AP recommend that women with this diagnosis receive one of the three main BPs or the biologic drug denosumab for 5 years, and they do not require BMD monitoring [15]. Teriparatide and Abaloparatide
(genetically engineered fragments of the parathyroid hormone molecule (1-34PTH)) belong to the anabolic therapy of AP.
The anabolic effect on the osteoblast is manifested by an increase in the lifespan of bone-forming cells, a decrease in their apoptosis, an increase in the differentiation of mesenchymal stem cells towards the osteoblast and, thus, an increase in bone formation [16, 17]. It is recommended to additionally use it in patients with severe AP, with a history of existing vertebral fractures, in people with an extremely high risk of low-traumatic fractures, in patients with ineffectiveness and/or intolerance of previous therapy. It is recommended to continue continuous treatment of OP with tableted BP for 5 years, intravenous BP for 3 years, the maximum studied duration of continuous BP therapy is 10 years; the maximum studied duration of continuous therapy with denosumab is 10 years; The maximum permitted therapy with teriparatide is 24 months. [18]. Menopausal hormone therapy
(MHT) is recommended for the prevention of AP in women under 60 years of age with a postmenopausal duration of up to 10 years.
If recommendations are followed and MHT is started on time, then it can be considered as first-line therapy. After 60 years, MHT is not advisable and carries certain risks. When prescribing hormone therapy, it is necessary to use the lowest effective doses and reduce the dose of the drug with increasing age [19, 20]. The Woman's Health Initiative (WHI) study found that the use of MHT for 5 years reduced the risk of developing vertebral and hip fractures by 34%, and non-vertebral fractures by 23% [21]. The global MHT study (WHI) demonstrated an increased risk of CAD, stroke, invasive breast cancer, PE, and deep vein thrombosis of the lower extremities over 5 years of treatment with standard doses of conjugated equiestrogens (CEE) and medroxyprogesterone acetate (MPA). However, a subsequent reanalysis of these data did not confirm an increase in the risk of coronary heart disease in women under the age of 60 years who began treatment in the first 10 years of postmenopause, while the increased risks of breast cancer, stroke and thromboembolism remained but were low [22]. Selective estrogen receptor modulators
(raloxifene, bazedoxifene) interact with estrogen receptors, which have a positive effect on bone tissue and do not increase the risk of breast cancer [23–25], cardiovascular complications and endometrial hyperplasia, but thromboembolic complications are possible [7, 26–28 ]. Their use prevents bone loss in the spine and hip in healthy postmenopausal women without AP, but does not increase BMD [29]. However, recent ACP guidelines do not recommend raloxifene for the treatment of AP due to the fact that it increases the risk of cardiovascular and venous thromboembolic events. All drugs for the treatment of AP are recommended to be prescribed in combination with calcium and vitamin D supplements.

Calcium and vitamin D

Considering that calcium is the main structural unit of skeletal bones (99% of all calcium in the body is contained in bone tissue), it plays a significant role in the prevention and treatment of AP (osteopenia). It is known that calcium requirements vary depending on age. The risk of fractures depends on two factors: the peak of bone mass in adulthood (at age 30) and the subsequent level of bone loss. To prevent AP, sufficient intake is necessary in childhood and adolescence, in women during pregnancy and the postpartum period, during peri- and postmenopause, and in old age. Age norms for calcium consumption (mg) [30]:
– children under 3 years old – 700; – children from 4 to 10 years old – 1000; – children from 10 to 13 years old – 1300; – teenagers from 13 to 16 years old – 1300; – persons over 16 and under 50 years old – 1000; – women in menopause or over 50 years old – 1000–1500; – pregnant and breastfeeding women – 1000–1300.

Calcium, which our body obtains naturally from food, is much more beneficial than dietary supplements, but due to the deterioration of food quality, we do not get even half of the daily requirement. Some countries even fortify commonly used products with calcium (cereals, juices, bread). It is also necessary to take into account the fact that children absorb up to 50–70%, and adults only 25–35% of calcium from food. The deficiency is aggravated by various diseases of the stomach and intestines that interfere with the absorption of calcium, which is quite common in old age. Data from epidemiological studies indicate that the daily calcium deficiency in the majority of the adult population is from 500 mg of calcium, which dictates the need to prescribe calcium medications, especially for patients with AP. Recent research suggests that calcium intake (1000 mg or more per day) may slow bone loss in postmenopause. This is most effective in women who have been postmenopausal for 5 years or more, as well as in patients whose diet was initially low in calcium and who had clinically proven AP. In a meta-analysis of 17 studies that lasted up to 3 years, more than 50 thousand patients received calcium alone or in combination with vitamin D. As a result of calcium supplementation alone, a 12% reduction in the risk of fractures of various sites, including the vertebrae, femur and forearm, was noted [31]. The recommended calcium intake in postmenopausal age is 1000–1500 mg/day and is indicated regardless of the presence of risk factors for AP and bone mass status. Ensuring sufficient calcium intake is also required during all therapeutic programs. This is primarily due to the hypocalcemic effect of most antiresorptive drugs (calcitonin, BP, ipriflavone), and on the other hand, a possible disruption of bone tissue mineralization when using fluorides, BP of the first generation. Calcium in a daily dose of 1000 mg and vitamin D in a dose of 800 IU should be a mandatory part of the treatment strategy for AP with all available antiresorptive drugs (BP, denosumab, hormone replacement therapy, selective estrogen receptor modulators) in the absence of hypercalcemia. Taking calcium after stopping therapy with osteoporotic drugs can, to a certain extent, slow down the reactive increase in bone resorption (the “rebound” phenomenon). Replenishing calcium deficiency by consuming calcium-containing products, especially for older people, sometimes becomes a difficult task, because to obtain 1000 mg of calcium from food it is necessary to take, for example, 1 liter of milk, 200 g of cheese, 300 g of cottage cheese, but such an amount may contain and high amounts of cholesterol [30, 32, 33]. In this regard, the use of calcium-containing drugs is most often recommended. Along with calcium preparations, the basis of therapy for AP are vitamin D preparations. In the presence of a sufficient amount of calcium, vitamin D is able to activate its absorption in the intestines by 70–80% and ensures mineralization of the skeleton. Vitamin D

is a group of steroid hormones that are formed in the body on the basis of vitamins D2 and D3 supplied with food and vitamin D3 synthesized in the skin under the influence of ultraviolet rays [34]. Vitamin D is an important regulator of bone metabolism and can also be associated with the development of cardiovascular and cancer diseases, diabetes mellitus, multiple sclerosis, etc.

Recommended daily intakes of vitamin D (IU/day) [35]:

– children 0–12 months. – 400; – children 1–17 years old – 600; – persons 19–50 years old – 600–800; – persons over 50 years old – 800–1000; – during pregnancy/lactation – 800–1200.

Doses to maintain 25(OH)D levels above 30 ng/ml in individuals with previously diagnosed low vitamin D levels are usually higher than prophylactic doses and amount to at least 1500–2000 IU of colecalciferol per day [36]. Low levels of vitamin D in the body can be caused by a violation of its synthesis, insufficient content in the diet, or limited exposure to the sun. One of the main causes of vitamin D deficiency worldwide is insufficient exposure to sunlight. In northern latitudes, vitamin D synthesis in the skin may be limited to six months. It is also important that in older people there is an age-related decrease in the ability of the skin to produce D3, as well as the fact that its absorption in the intestines decreases with age [37, 38]. Postmenopause and age-related estrogen deficiency also affect the absorption of vitamin D. It has been proven that in the intestine, estrogens interact with vitamin D metabolites. Estrogens have a stimulating effect on the expression of the vitamin D receptor on the surface of the intestinal epithelial cell, which is involved in the transport of calcium through the mucosa. Thus, the negative impact of vitamin D deficiency on the bone health of elderly patients is increased due to a deficiency of estrogens responsible for the expression of the 1,25(OH)2D3 receptor. Long-term low levels of vitamin D can lead to insufficient absorption of calcium in the intestine, resulting in the development of secondary hyperparathyroidism with increased mobilization of calcium from the bones, the development of AP, in some cases in combination with osteomalacia. Vitamin D supports the formation and metabolism of muscle tissue, especially at the level of fast-twitch muscle fibers (there is an increased risk of falls in individuals with a deficiency of this vitamin). The administration of D3 with calcium leads to increased muscle strength and coordination of movements and reduces the incidence of fractures from falls in the elderly [ 39, 40]. Complete replenishment of vitamin D deficiency with food is not always possible, since it is found mainly in fatty fish (herring, mackerel, salmon), fish oil, liver and fat of aquatic mammals [30, 41]. Prevention of vitamin D deficiency is recommended with the use of active metabolites of vitamin D: colecalciferol (D3) and ergocalciferol (D2). In treatment programs, vitamin D deficiency is replenished only with the drug colecalciferol, which is recommended in elderly patients with a high risk of falls as monotherapy or in combination with antiresorptive therapy. The daily dose of vitamin D should be at least 800 IU [18]. The combination of calcium with vitamin D reduces the risk of all fractures by 12% (p=0.025), and the risk of hip fractures by 26% (p=0.005) [42].

How to make up for the deficit?

Modern calcium-containing supplements can be mono- or combined preparations, contain only vitamin D, microelements, or be complex vitamin preparations. However, the latter are characterized by the presence of a small dose of calcium in the composition, and monopreparations require mandatory supplementation with vitamin D. There are several types of calcium. Calcium carbonate
reduces the secretion of gastric juice (buffering effect), can cause flatulence, constipation, nausea and abdominal pain and is not recommended for patients with reduced secretion.
And, as is known, elderly patients suffering from AP, as a rule, have a “bouquet” of gastrointestinal diseases, including atrophic diseases. Calcium citrate
(calcium citrate).
Calcium citrate is a chemical compound of calcium salts and citric acid. The degree of absorption of calcium citrate is 44% and 2.5 times higher than that of carbonate. It does not require hydrochloric acid from the gastric juice for its absorption. Therefore, it is preferable for elderly people suffering from atrophic diseases of the gastrointestinal tract, and causes dyspeptic symptoms to a lesser extent than other calcium salts. A study of postmenopausal women found that calcium citrate, compared with carbonate, not only provided a higher peak rise in blood calcium levels, but also significantly reduced urinary calcium excretion. In addition, calcium citrate led to a greater decrease in parathyroid hormone levels, the same hormone that flushes calcium from bones. Calcium chelate. Amino acid chelates also have high bioavailability, fewer side effects, and their use does not form kidney stones, but their price is an order of magnitude higher than the price of calcium citrate. An ideal drug for the treatment and prevention of AP should contain a sufficient amount of easily digestible calcium and vitamin D and should be affordable, taking into account the duration of its use. In addition, given that in old age the absorption and often adequate supply of many vital microelements from food is impaired, it is desirable that it include both macro- and microelements. One of these drugs is Calcemin Advance, 1 tablet of which contains 500 mg of calcium in the form of its salts - citrate and carbonate, vitamin D3 (cholecalciferol) 200 IU and osteochondroprotective micro- and macroelements necessary for the normal development and functioning of bone and cartilage tissue: zinc (7.5 mg), copper (1 mg), manganese (1.8 mg), boron (250 mcg) and magnesium (40 mg). Zinc, which is part of Calcemin, ensures the activity of more than 200 enzymes, including alkaline phosphatase. Manganese normalizes the synthesis of glycosaminoglycans necessary for the formation of bone and cartilage tissue. Boron regulates the activity of parathyroid hormone, which is responsible for the metabolism of calcium, magnesium, and phosphorus. Thus, boron helps normalize bone tissue metabolism regardless of vitamin D. The magnesium contained in the preparation is an additional factor in increasing the bioavailability of calcium and relieves cramps in the lower extremities in patients with AP. Copper is involved in the synthesis of collagen and elastin, preventing bone demineralization. Collagen plays a critical role in the retention of calcium in bone tissue, being the main component of the organic bone matrix. A necessary condition for restoring bone structure during bone regeneration in postmenopausal and drug-induced AP, healing of fractures, as well as other disorders of bone integrity is improving collagen biosynthesis. Calcemin Advance promotes the synthesis of the collagen matrix and saturation of bone tissue with essential micro- and macroelements, and also stops the leaching of calcium, preserving the strength of bone tissue. The effectiveness of the drug Calcemin Advance for the treatment of postmenopausal AP has been confirmed in various studies. Thus, an open controlled study was conducted to study the effectiveness and tolerability of the complex drug Calcemin Advance for osteopenia in postmenopausal women in comparison with women who corrected the deficiency by taking calcium carbonate. When analyzing BMD indicators, it was found that in patients of the 1st group who took Calcemin Advance, there was at least a preservation of the initial BMD in the study area or its increase (the increase in bone mass amounted to an average of 3.55%), while in patients Group 2, taking calcium carbonate, showed negative dynamics (decrease in BMD in the study area by 1.02%) after 12 months. therapy [43]. In another observation (A.M. Lila), the effectiveness of the use of the drug Calcemin Advance for the prevention of AP during the postmenopausal period was proven. Women aged 45–65 years with 2 or more risk factors for the development of AP who received therapy with Calcemin Advance showed a stable state of BMD, while in the control group BMD decreased in all assessed areas, which was especially pronounced in the lumbar spine, and this decrease was significant [44, 45]. In a 3-year multicenter clinical study, women receiving Calcemin Advance, after 12 months. observations in the treatment group had stable BMD, decreased pain and improved daily activity compared to the control group, where nutritional correction was carried out. In all observations, good tolerability and bioavailability of the drug, and the absence of significant adverse events were noted. The high effectiveness of the drug Calcemin Advance has been established in trauma patients with signs of AP [7, 46, 47]. The results obtained indicate the effectiveness of long-term therapy with the combination drug Calcemin Advance in the treatment and prevention of postmenopausal AP; the use of the drug contributes not only to stabilization, but also to an increase in BMD. The established good tolerability of Calcemin Advance during its long-term use is important [48]. It should also be noted that currently preference is given to calcium preparations containing minerals. Calcemin Advance, unlike other drugs, contains calcium and minerals that form a collagen network, which retains calcium in the bones and, therefore, increases bone mineral density. In a 52-week open-label pilot study evaluating the effects of Calcemin Advance and intravenous zoledronic acid compared with other calcium and intravenous zoledronic acid in 38 patients with postmenopausal AP aged 50 to 65 years, it was found that after 12 months. the increase in BMD at L1-L4 was significantly higher in the group receiving Calcemin Advance. Also in this group, the intensity of the pain syndrome significantly decreased and hypercalciuria was not detected, in contrast to the comparison group [49]. Preventive treatment should be started in all postmenopausal women who have 2 or more risk factors for AP. It is advisable to take Calcemin Advance 2 times a day, since in low doses there is better absorption of calcium. The drug is best taken at lunchtime and in the evening (during meals), which prevents accelerated loss of calcium in the second half of the night due to circadian acceleration of bone resorptive processes. Given its good tolerability, the drug can be prescribed long-term, both as monotherapy and in combination with other anti-osteoporotic drugs.

What diet is necessary for osteoporosis?

The diet for osteoporosis has no special secrets - you just need to ensure sufficient intake of vitamin D and calcium into the body, which are necessary for the formation of new bone tissue. The richest foods in calcium are dairy products, fish, cabbage (including broccoli), and various nuts. The main source of vitamin D in the body is fish (or fish oil). Significant amounts of vitamin D are produced in the skin when exposed to sunlight.

At the same time, when planning nutrition for osteoporosis,

It should be remembered that dietary “exercises” alone are not able to eliminate either calcium deficiency or vitamin D deficiency. In the vast majority of cases, diet is only one element of the treatment of osteoporosis and must be accompanied by taking calcium and vitamin D supplements in the form of tablets - this is the only way eliminate long-term chronic vitamin D deficiency.

Disease prevention

To prevent the development of early osteoporosis, it is recommended to follow the following preventive measures:

Adhere to the principles of proper nutrition. Include a large number of foods in your diet that contain calcium, phosphorus, and magnesium. As prescribed by the doctor, take medications that contain calcium and vitamin D. Be sure to increase the concentration of these substances during pregnancy, menopause, and breastfeeding.
Include physical and sports activities and therapeutic exercises in your daily regimen.
Stop smoking and drinking alcohol. Minimize stress and the amount of fast food.
Be very careful when taking medications for a long time, under the influence of which calcium is washed out of the body. If it is not possible to refuse to take them, you need to monitor calcium and magnesium levels in the body.

It is important to consult a doctor promptly when the first suspicious symptoms appear. You should not ignore signs that may indicate the development of destructive processes in the musculoskeletal system.

Complications of osteoporosis

The main and most dangerous complication of osteoporosis is fractures. The most dangerous fractures are fractures of the vertebrae and femoral neck. At the moment, it is “thanks to” hip fractures that osteoporosis is in fourth place among the causes of death in the world (second only to vascular diseases, oncology, and diabetes mellitus). Osteoporosis of the spine leads to the development of compression fractures even when exposed to minor loads (for example, when falling from your own height, or when landing after a jump). It is important to understand that immobility following a fracture of the spine or femoral neck in a significant number of cases ends in bedsores, congestive pneumonia, infectious complications, and thrombosis. Only early surgical treatment can reduce mortality from hip fractures, but, unfortunately, it cannot be performed in many elderly patients due to the presence of severe concomitant pathology. Osteoporosis of the spine cannot be corrected by surgery at all. That is why the only effective method of treating osteoporosis is early diagnosis and combined conservative therapy - this is the only way to avoid the development of fractures.

How is osteoporosis prevented?

Prevention should include several areas aimed at eliminating the previously listed risk factors for osteoporosis.

It is important to ensure sufficient intake of calcium and vitamin D from food - for this you should eat dairy and other calcium-rich foods listed above. You should reduce your consumption of alcohol and caffeine-containing drinks and foods.

There are a number of scientific studies showing that long-term use of calcium and vitamin D supplements for the purpose of prevention can reduce the risk of developing osteoporosis. Taking moderate doses of calcium with vitamin D for 3-4 years does not lead to side effects, but can improve bone density. It is enough to take calcium carbonate in a dose of 500 mg with 200 IU of vitamin D twice a day (for example, calcium D3 Nycomed, 1 tablet 2 times a day; or Calcemin-Advance, also 1 tablet 2 times a day). Taking calcium and vitamin D supplements is safe even if you have urolithiasis. However, the issue of preventive therapy should still be decided after consulting an endocrinologist.

Physical activity is the next factor to prevent the development of osteoporosis. Prevention using physical activity can increase the load on the bone and stimulate its strengthening.

For women during menopause, an important factor in the prevention of osteoporosis is the use of hormone replacement therapy, which allows them to “imitate” normal ovarian function for a long time and reduce the risks associated with the extinction of the natural hormonal function of the ovaries. Such therapy is also an effective factor in the treatment of osteoporosis, if it has already occurred. Of course, the selection of treatment is carried out by an endocrinologist.

One should not forget about the need to monitor thyroid function if the development of osteoporosis is suspected. To do this, it is enough to perform an ultrasound of the thyroid gland and pass a basic set of tests (usually for the first examination it is enough to donate blood for TSH, T4 free, and antibodies to thyroid peroxidase). When taking tests, do not forget about the need to monitor the level of ionized calcium annually! Timely detection of an increase or decrease in blood calcium levels greatly facilitates treatment.