Terms and Definitions
Osteoporosis
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 [1].
Minimal trauma
— a fall from one’s own height onto the same surface or even lesser injury [2, 3].
Low-traumatic (low-energy) or osteoporotic fracture is a bone fracture that occurs with minimal trauma, in the vast majority of cases developed as a result of osteoporosis. Some experts suggest using the term pathological fracture
, i.e., a fracture due to a disease rather than a traumatic effect, for example, a fracture in patients with metastatic skeletal lesions, a fracture due to Paget's disease, etc. A fracture due to osteoporosis can also be classified as a pathological fracture. However, further for unification the term “low-traumatic fracture” will be used.
Severe osteoporosis
- osteoporosis with a history of low-traumatic fracture of the vertebral body (s), hip fracture or multiple fractures, regardless of the degree of decrease in bone mineral density (BMD) according to densitometry.
Fractures of the phalanges of the fingers and skull bones, regardless of the nature of the injury, are not considered fractures due to osteoporosis.
Etiology and pathogenesis
Osteoporosis is a polyetiological disease, the development of which depends on genetic predisposition, lifestyle, physical activity, endocrinological status, the presence of concomitant diseases, medication use, human aging and individual life expectancy [4]. Bone mass gain occurs in childhood and adolescence, reaching a maximum by 20-30 years. After reaching a peak until the age of 35-40, bone mass remains almost unchanged, after which it begins to gradually decrease. In women, the rate of decrease in BMD is significantly higher than in men, which is due to estrogen deficiency during peri- and postmenopause.
Bone tissue is in a constant state of change. Two opposing processes occur simultaneously: bone formation and bone resorption, the balance of which determines BMD, bone quality and strength. In conditions of estrogen deficiency, this balance shifts towards bone loss. However, estrogen deficiency is not the only cause of loss of BMD, as previously thought. Bone tissue remodeling depends on the state of phosphorus-calcium metabolism, levels of parathyroid hormone, vitamin D, growth hormone, calcitonin, thyroid hormones, glucocorticoids, etc. In general, all effects on the state of bone tissue metabolism are realized through the main regulatory systems of osteoblastogenesis (canonical wnt -signaling pathway) and osteoclastogenesis (RANKL/RANK/OPG). Changes in the expression of molecules that regulate osteoblastogenesis and osteoclastogenesis with age and due to the negative influence of other factors lead to a decrease in bone strength, which can be manifested by a decrease in bone mass, BMD and/or disruption of internal microarchitecture and, as a consequence, fractures with minimal trauma [5].
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Epidemiology and social significance of osteoporosis
In Russia, among people aged 50 years and older, osteoporosis is detected in 34% of women and 27% of men, and the incidence of osteopenia is 43 and 44%, respectively. The incidence of osteoporosis increases with age [6]. Osteoporosis affects approximately 14 million people and another 20 million people have a decrease in BMD corresponding to osteopenia [7]. Similar rates of osteoporosis prevalence in women were noted among the white population of North America and a number of Western European countries [5, 8].
The social significance of osteoporosis is determined by its consequences - fractures of the vertebral bodies and bones of the peripheral skeleton, leading to large material costs in the field of health care and causing a high level of disability, including disability and mortality.
The most common fractures due to osteoporosis are those of the proximal femur, radius, and vertebral bodies, but fractures of other large skeletal bones (pelvis, ribs, sternum, tibia, humerus, etc.) are also common [9]. A cross-sectional epidemiological study among the urban population of Russia showed that 24% of women and 13% of men aged 50 years and older had previously had at least one low-traumatic fracture, with vertebral body fractures being the most common [10]. The prevalence of low-traumatic vertebral body fractures is about 10% in men and 12.7% in women [7]. The incidence of femoral neck fractures, according to an epidemiological study conducted in 16 cities of Russia (the total population aged 50 years and older was 1,749,274 people) in 1992-1997, was 100.9 per 100,000 population, while these fractures were recorded significantly more often among women (115.5/100,000) compared to men (77.0/100,000; p
<0.0001) [6]. The incidence of fractures was lowest in people of both sexes aged 50-54 years and increased smoothly until the age of 65 years, and then its exponential growth was noted, especially pronounced in women. Over a 5-year period of fracture registration, there was an increase in the incidence of hip fractures in both women and men [6]. A similar study was conducted 11 years later (2008-2009) in 4 cities of Russia. It showed that the incidence of proximal femur fractures is already 239 cases per 100,000 population (276 and 175 cases in women and men, respectively). Moreover, in men aged 50–64 years it was 2 times higher than in women, and at the age of 75 years and older this trend was diametrically opposite [10].
Mortality rates within 1 year after hip fracture range from 12 to 40%, with this rate being higher in men [9]. Mortality is especially high during the first 6 months after a fracture, which is 5-20% higher compared to this indicator in people of the same age without fractures, and in some cities of Russia the mortality rate was 8 times higher than the citywide mortality rates in people of the same age [ eleven]. In patients who have suffered low-traumatic fractures, the quality of life is significantly reduced, which is only partially restored after an average of 12–24 months, depending on the location of the fracture [11]. Thus, among people who survive a hip fracture, every third person loses the ability to self-care and needs long-term constant care. Restoration of quality of life in surviving patients who have suffered a fracture of the proximal femur occurs on average after 2 years and depends on whether surgical treatment was performed.
A fracture of the distal forearm is one of the most common types of fractures caused by a fall from one's own height. According to an epidemiological study, in Russia its incidence was 426 per 100,000 population, exceeding the incidence of hip fracture by 3-7 times in men and 4-8 times in women and significantly prevailing in women.
Moreover, over a 5-year period, there was a significant increase in the incidence of fractures of any location, especially in patients who had already suffered a fracture [6].
The average cost of 1 year of treatment for osteoporosis complicated by a fracture was 61,151 rubles, with the most expensive treatment for patients with a fracture of the proximal femur, and the least costly for a fracture of the distal forearm [12]. Taking into account epidemiological data on the frequency of low-traumatic fractures, recalculation for the Russian population aged 50 years and older showed that only direct medical costs for the treatment of low-traumatic fractures of five main locations in one year can reach about 25 billion rubles, while the costs of treating patients with vertebral body fractures, which occur in approximately 10% of the population aged 50 years and older, are almost 2 times higher than the cost of treating patients with a hip fracture nationwide [12].
A comparative study of the social and economic consequences of a hip fracture and myocardial infarction [13] showed that with the same treatment costs for these two diseases, patients with a fracture have a significantly lower quality of life, primarily due to the lack of surgical treatment or poor rehabilitation, and, as consequence, chronic pain syndrome and movement disorders.
Taking into account the projected increase in life expectancy in Russia, in the coming years there will be an increase in cases of low-traumatic fractures. For example, by 2035, the number of cases of proximal femur fractures will increase by 36% in men and by 43% in women [14].
Thus, the high and constantly growing prevalence of osteoporosis, the significant cost of treating both the disease itself and its direct complications - fractures, the development of pain, deformities and loss of ability to work and the ability to self-care, determine the importance of this problem for the healthcare of the Russian Federation.
Coding according to ICD-10
M80.0 - Postmenopausal osteoporosis with pathological fracture:
M80.1 - osteoporosis with pathological fracture after removal of the ovaries;
M80.2 - osteoporosis with pathological fracture caused by immobility;
M80.3 - post-surgical osteoporosis with pathological fracture caused by malabsorption in the intestine;
M80.4 - drug-induced osteoporosis with pathological fracture;
M80.5 - idiopathic osteoporosis with pathological fracture;
M80.8 - other osteoporosis with pathological fracture;
M80.9 - osteoporosis with pathological fracture, unspecified;
M82.1* - osteoporosis due to endocrine disorders (E00-E34+).
M81.0 - Postmenopausal osteoporosis:
M81.1 - osteoporosis after oophorectomy;
M81.2 - osteoporosis caused by immobility;
M81.3 - post-surgical osteoporosis caused by malabsorption;
M81.4 - drug-induced osteoporosis;
M81.5 - idiopathic osteoporosis;
M81.8 - other osteoporosis;
M81.9 - osteoporosis, unspecified.
An additional external cause code (class XX) is used to identify the drug.
Classification
Primary osteoporosis
develops as an independent disease without identifying another cause of decreased skeletal strength, occupies 95% of the structure of osteoporosis in postmenopausal women (postmenopausal osteoporosis) and 80% of the structure of osteoporosis in men over 50 years of age [4, 5, 8, 15]. Primary osteoporosis also includes idiopathic osteoporosis, which develops in women before menopause, men under 50 years of age, and juvenile osteoporosis, which is diagnosed in children (up to 18 years of age). Idiopathic and juvenile forms of primary osteoporosis are extremely rare.
Secondary osteoporosis
develops as a result of various diseases or conditions, as well as taking medications, i.e. there is a specific cause leading to osteoporosis (Table 1).
Table 1. Conditions, diseases and drugs that can lead to the development of secondary osteoporosis [15] Note. *Osteogenesis imperfecta, hyperparathyroidism, myeloma, hypophosphatasia are metabolic diseases with predominantly skeletal involvement and therefore can be considered as independent diseases.
Table 1. Conditions, diseases and drugs that can lead to the development of secondary osteoporosis [15] Note.
*Osteogenesis imperfecta, hyperparathyroidism, myeloma, hypophosphatasia are metabolic diseases with predominantly skeletal involvement and therefore can be considered as independent diseases. In the structure of osteoporosis, secondary osteoporosis occupies 5% in women and 20% in men [15]. The development of mixed osteoporosis is possible. For example, when taking glucocorticoids in postmenopausal women due to a serious somatic disease, which in itself can lead to the development of secondary osteoporosis.
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Diagnostics
Complaints and anamnesis
Before the development of a low-traumatic fracture, osteoporosis has no clinical manifestations.
In this regard, at the stage of collecting complaints and anamnesis, it is first necessary to assess the individual 10-year probability of a low-traumatic fracture using the FRAX (Fracture Risk Assessment Tool) algorithm. FRAX is endorsed by WHO and is available as a free resource online (https://www.shef.ac.uk/FRAX/?lang=rs). It is convenient for a practicing physician to find out the most important details of the medical history by immediately including them in the FRAX fracture probability analysis, in the model developed for Russia: https://www.shef.ac.uk/FRAX/tool.aspx?country=13.
Recommendation 1.
Screening to identify groups at high risk of fracture
is recommended
using the FRAX algorithm among all postmenopausal women and men over 50 years of age (A1).
Comments.
Due to the high prevalence of osteoporosis and low-traumatic fractures in older age groups [4, 5, 8], the severe disabling consequences of low-traumatic fractures, the high costs of fracture treatment and subsequent rehabilitation [7, 9-12], screening to identify patients at high risk of fractures is justified. in order to prevent them. The risk factors for major osteoporotic fractures and for hip fracture included in the FRAX algorithm were identified from 12 prospective cohort studies in multiple geographic regions using primary databases [1, 16], providing a high degree of evidence for the use of the algorithm. The follow-up period was 250 thousand patient-years among 60 thousand men and women, during which more than 5000 fractures were recorded [16]. Each risk factor included in the FRAX algorithm increases the likelihood of fractures regardless of BMD, but can be combined with BMD measurement in an individual patient [1, 8, 16]. Key risk factors for low-traumatic fractures that have proven their independent contribution are summarized in Table. 2.
Table 2. Risk factors included in the WHO Fracture Probability Assessment Model (FRAX) [8] Note: From WHO Technical Report [1].
During a survey using the FRAX algorithm, along with other risk factors, the doctor specifies the presence of a fracture in the anamnesis. If the answer to this question is positive, it is necessary to clarify the location of the fracture and the nature of the injury [1].
Recommendation 2.
In the presence of low-traumatic fractures of large skeletal bones (femur, vertebral body(s), multiple fractures),
it is recommended
to establish a diagnosis of osteoporosis and prescribe treatment regardless of the results of densitometry or FRAX (subject to the exclusion of other skeletal diseases) (A1).
Comments.
A low-traumatic fracture is a key complication of osteoporosis, which combines a decrease in bone mass and a violation of microarchitecture, while X-ray densitometry reflects only a decrease in bone mineral density and is one of the risk factors for fractures. Regardless of BMD, age and other clinical risk factors, radiologically confirmed fractures of the vertebral bodies (even if they are completely asymptomatic), fractures of the femur and other large skeletal bones are a sign of changes in the structure and decrease in bone strength and a significant predictor of new fractures of the vertebral bodies and other skeletal bones [8, 9], therefore, the presence of a fracture with minimal trauma is sufficient to establish a diagnosis of osteoporosis and prescribe treatment [1, 5, 8]. However, a necessary condition for establishing the diagnosis of osteoporosis is the exclusion of other metabolic skeletal diseases [5].
Unlike osteoporosis, a low-traumatic fracture in the acute period, as a rule, has a clear clinical picture. A fracture is associated with pain, dysfunction and is diagnosed x-ray by a traumatologist, who, depending on the nature of the previous injury, may suspect osteoporosis.
The clinical manifestations of low-traumatic vertebral body fractures, which may remain undiagnosed for a long time, deserve special attention. Compression fractures of the vertebral bodies are accompanied by pain or a feeling of fatigue in the back, decreased height, and also, in the case of the development of multiple compression deformities, a number of clinical manifestations presented in Fig. 1.
Rice. 1. Clinical manifestations of multiple compression deformities of the vertebral bodies.
Physical examination of the patient
Measuring the patient's height and weight and calculating the body mass index.
When recording height results, it is necessary to clarify the maximum height at a young age (25 years) and/or at the last previous height measurement. If height decreases by 2 cm or more over 1-3 years or by 4 cm or more over a lifetime, compression fracture(s) of the vertebral body should be suspected.
The presence of folds of skin on the back and sides (symptom of “excess skin”), a decrease in the distance between the costal arches and the iliac crests less than the width of 2 fingers are physical signs of compression fractures of the vertebral bodies.
When measuring height, you should pay attention to the inability to fully straighten up, the appearance of a distance from the wall to the back of the head, which is a symptom of compression fractures of the vertebral bodies.
For characteristic kyphotic deformation of the chest, a relative increase in volume of the abdomen (“protrusion” of the anterior abdominal wall), relative lengthening of the limbs and shortening of the chest, see
rice. 1 and are symptoms of multiple compression deformities of the vertebral bodies.
In addition, during a physical examination, attention should be paid to the presence of symptoms of diseases leading to secondary osteoporosis (see Table 1), which are quite specific for each pathology.
Instrumental diagnosis of osteoporosis
Recommendation 3.
For patients with back pain, a decrease in height by 4 cm over a lifetime or by 2 cm with regular medical monitoring, taking glucocorticoids, patients with long-term uncompensated T2DM or on insulin therapy, as well as diagnosed fractures of other locations, a
standard X-ray examination of the thoracic and lumbar spine is recommended. parts of the spine (Th4—L5) in the lateral projection to identify compression fractures of the vertebral bodies (B1).
Comments.
Compression fractures of the vertebral bodies can occur without significant pain. In addition, the clinical manifestations of the fracture are nonspecific and can be regarded as an exacerbation of radicular syndrome. However, up to 20% of patients who have experienced a low-traumatic vertebral body fracture will suffer a second fracture within the next year [17, 18]. Therefore, it is necessary to actively identify compression fractures of the vertebral bodies with referral for examination of patients in whom the likelihood of a fracture is high. The use of glucocorticoids and T2DM are the most significant risk factors for the development of vertebral compression fractures [15, 19—21], so these patients should be actively examined. After the first study, dynamic monitoring should be carried out only in cases of documented prospective decline in height or in the occurrence/recurrence of back pain or changes in posture [21, 22]. Repeated X-ray examination of the spine is also recommended in patients when deciding whether to discontinue drug treatment for osteoporosis, since in patients with recent fractures of the vertebral bodies, discontinuation of medications is undesirable.
Application of X-ray imaging methods of the spine
The condition of the vertebrae is assessed using radiography of the thoracic and lumbar spine in a lateral projection or using X-ray morphometry as part of routine densitometry (VFA - vertebral fracture assessment) [23]. Standard x-ray equipment is used to perform radiography. Obtaining lateral radiographs of the thoracic (Th4—Th12) and lumbar (L1—L4) spine requires compliance with a number of rules [24, 25]:
- position of the patient on the left side;
- mandatory straightening of the scoliotic curvature of the spine with special foam rollers so that the line drawn along the spinous processes runs parallel to the table;
— use of a special breathing mode for radiography of the thoracic spine; a picture of the lumbar region is taken while holding your breath;
— it is advisable to use X-ray cassettes with special leveling screens for radiography of the spine.
Methods for assessing vertebral body fractures
A compression fracture of a vertebral body is a decrease in the height of a vertebral body (compression deformity) in the anterior, middle or posterior sections by 20% or more compared to other sections of the same vertebra [22].
The classification of grades 0, 1, 2 and 3 fractures is shown schematically in Table. 3.
Table 3. Method for assessing compression deformities of the vertebral bodies [22, 24]
Recommendation 3.1.
Practitioners
are not recommended
to make a diagnosis of osteoporosis based on indirect signs of increased transparency of skeletal bones on standard radiographs in patients without compression fractures of the vertebral bodies (B1).
Comments.
The radiologist's report may indicate signs of osteoporosis when x-raying various parts of the skeleton. The main radiological symptom of osteoporosis - increased radiolucency of bone tissue - is nonspecific and largely depends on the technical conditions of shooting and the quality of development of radiographs [4]. In the absence of characteristic compression deformities of the vertebral bodies (compression fractures), establishing a diagnosis of osteoporosis based on radiographic data is inappropriate [4].
Multislice tomography (MSCT), magnetic resonance imaging (MRI) and skeletal scintigraphy can be considered as additional methods of differential diagnosis [26–29].
FRAX as a tool for selecting patients in need of osteoporosis therapy
As a result of the FRAX calculation, the physician receives the individual 10-year probability of hip fracture (%) and major low-trauma fractures (%). The term “major low-traumatic fractures” in this case combines clinically significant fractures of the vertebral bodies (i.e., fractures that are accompanied by pain), fractures of the hip, humerus and radius [1, 8, 15].
Recommendation 4.
It is recommended to establish a diagnosis of osteoporosis and prescribe treatment for patients with a high individual 10-year probability of major low-traumatic fractures (the FRAX assessment result corresponds to the Russian threshold for intervention (Fig. 2)
Figure 2. FRAX intervention point proposed for the Russian population based on data from studies in Yaroslavl and Pervouralsk (BMI 24 kg/m2), without BMD data.
regardless of the densitometry index (C2). Comments.
When calculating the individual 10-year probability of a fracture, the FRAX algorithm takes into account the probability of death from other causes [1]. The likelihood of low-traumatic hip fracture and mortality vary markedly in different regions of the world [30], so the FRAX algorithm is calibrated for those countries where the epidemiology of low-traumatic hip fractures and mortality rates are known [31].
The threshold for therapeutic intervention, i.e. the individual probability of fracture at which it is justified to begin treatment, remains a subject of debate and discrepancy in many countries. This question depends, among other things, on the country’s material capabilities and the share of gross domestic product that is spent on health care, as well as on the treatment and prevention of fractures.
For example, in the United States, a 10-year probability of 3% for hip fractures and 20% for major osteoporotic fractures is considered cost-effective for initiating osteoporosis therapy [5].
Before the advent of FRAX, many clinical guidelines in Europe, North America, and other countries recommended starting treatment in the absence of BMD information in patients with a low-traumatic fracture, especially if it is a vertebral body fracture or a hip fracture [8, 16, 32]. For this reason, the threshold for intervention in women without a fracture may be set to be equivalent to the probability of fracture in women with a previous low-traumatic fracture [31–34]. The same intervention threshold is recommended for men, as the clinical and cost-effectiveness of the intervention in men is similar to that in women with an equivalent risk of fracture [1, 8].
In the European Clinical Guidelines for the Diagnosis and Treatment of Osteoporosis in Postmenopausal Women, a cumulative intervention threshold was constructed based on population data on fractures and life expectancy in five countries (Spain, France, Germany, Italy, UK) [8]. The average probability of major low-trauma fractures was weighted by population size at each age interval in each country. The likelihood of fracture increases with age, which has been accepted as a threshold for intervention [8]. The choice of intervention threshold also depends on the availability of densitometry. For those countries where the number of densitometers is less than 1 per 1,000,000 population, we can talk about an insufficient number of densitometers. In this case, it is advisable to identify a group of patients with an average risk, which is optimally referred for densitometry, while those with a low or obviously high risk of fractures do not need to be sent for densitometry. Thus, the concept of an intervention point and a lower and upper threshold for intervention appears. Patients who fall into the category with a fracture probability above the upper threshold for intervention should be referred for treatment, and those with a probability of fracture below the lower threshold for intervention do not require treatment. Those patients whose fracture likelihood is between the lower and upper intervention thresholds are referred for x-ray osteodensitometry, and their fracture likelihood is reestimated depending on the densitometry result at the femoral neck. The European intervention point, lower intervention threshold and upper intervention threshold averaged over 5 countries with different fracture probabilities are summarized in Table. 4.
Table 4. FRAX intervention point for 10-year probability (%) of major osteoporotic fractures, equivalent to the probability of fractures in women with a history of fragility fracture without other risk factors (BMI = 24 kg/m2), without BMD data [8] Note . 1The point of therapeutic intervention is the value of the individual 10-year probability of major low-traumatic fractures, at which a patient of the appropriate age, based on a combination of risk factors, is indicated to begin therapy for osteoporosis (X-ray densitometry can be performed only for dynamic assessment of the effectiveness of treatment). 2Low probability of fractures - the value of the individual 10-year probability of major low-traumatic fractures, at which (and at lower values) X-ray densitometry is not indicated for a patient of the appropriate age based on a combination of risk factors and the patient does not need treatment for osteoporosis. 3High probability of fractures - the value of the individual 10-year probability of major low-traumatic fractures, at which (and at higher values) X-ray densitometry is not indicated for a patient of the appropriate age based on a combination of risk factors and the patient clearly needs treatment for osteoporosis.
The intervention point for the Russian population was proposed by the Russian Association of Osteoporosis (RAOP) based on statistical data obtained from trauma clinics in Yaroslavl and Pervouralsk [14, 35], and then refined by proposing the lower and upper limits of the intervention point (see Fig. 2) .
When comparing the patient's age (along the X-axis) and the individual 10-year probability of major low-traumatic fractures obtained by entering individual patient data into the FRAX algorithm (along the Y-axis), in the intersection zone the doctor receives information that the patient does not need treatment (green zone), the patient should be referred for densitometry (orange zone) or recommended treatment (point of intervention and above, red zone).
However, according to an independent Russian cohort study [36], the sensitivity of the Russian intervention point (FRAX) does not exceed 30%. In addition, when introducing the T-criterion into the algorithm, BMD at the femoral neck is not recommended, according to the Russian intervention point, treatment of osteoporosis for patients without other risk factors of all age categories with a T-criterion of -2.5 SD at the femoral neck, including when recalculating FRAX after receiving densitometry data. Thus, the selected FRAX intervention point for the Russian population is significantly inferior in sensitivity to X-ray densitometry.
It should be noted that both the epidemiological studies that formed the basis for the development of FRAX and the data from the prospective cohort on which the Russian intervention point was assessed do not have sufficient statistical power to match those of UK or European Union country-level epidemiological studies [8]. . In this regard, the use of an average European intervention point may be justified until more reliable data are obtained in the Russian population. In addition, individuals in whom FRAX densitometry testing was recommended (orange zone) and diagnosed with osteoporosis according to WHO criteria (T-score ≤–2.5 SD) should be advised to treat osteoporosis without reassessing FRAX.
FRAX Limitations
FRAX is not designed for use in young adults (under 40 years of age) or children. The FRAX tool has not been validated in patients who have previously received or are currently receiving pharmacotherapy for osteoporosis. However, patients who stopped taking medications 2 years ago or more may be considered untreated [37]. FRAX can be calculated by including BMD (T-score) at the femoral neck and does not take into account BMD of the lumbar spine. The WHO determined that for many secondary causes of osteoporosis, the risk of fracture was primarily due to the effect of the underlying disease on BMD [16]. For this reason, when BMD at the femoral neck is included in the online FRAX calculation, the flagged values for “secondary causes of osteoporosis” are automatically inactivated. The algorithm for estimating the 10-year probability of fracture has limitations that require the clinician's clinical judgment. Thus, if a patient has multiple fractures, the risk of subsequent fractures will be underestimated by the FRAX tool. In such patients, treatment for osteoporosis is prescribed regardless of the FRAX score. FRAX does not take into account the dose of glucocorticoids, the number of cigarettes and the amount of alcohol. The recalculation of the individual 10-year probability of fractures depending on the dose of glucocorticoids is summarized in table. 5 [8].
Table 5. Average recalculation of the 10-year probability of hip fracture and major osteoporotic fractures in postmenopausal women and men depending on the dose of glucocorticoids [8]
FRAX does not include some secondary causes of osteoporosis, such as T2DM, or the risk of falls.
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