My grandmother's bones
Test yourself for strength
Korolev Maxim Alexandrovich,
Candidate of Medical Sciences, head. Laboratory of the Research Institute of Clinical and Experimental Lymphology of the Institute of Cytology and Genetics SB RAS (Novosibirsk).
With age, our bone tissue becomes thinner, becomes brittle, and bones can break even in the case of a small load. The insidiousness of osteoporosis, which today is called the "quiet epidemic of the XXI century", is that the processes of pathological bone changes are not accompanied by pain, and the disease can progress asymptomatically for decades – until the first fracture. Is it possible to diagnose osteoporosis at an early stage? How to avoid the terrible consequences of pathological changes in bone tissue? In other words, can we help ourselves and our grandmother?
The main process that constantly occurs throughout life in the tissues of our skeleton is bone remodeling, replacing the old with a new one. There are three main types of cells involved in this continuous renewal: osteoclasts (they "eat" old bone), osteoblasts (they develop a new one) and osteocytes – the "bricks" of which the bone itself consists. Calcium, contained in bones in the form of the mineral hydroxyapatite (it also contains a large amount of phosphorus), plays the role of intercellular "concrete", strengthening the bone structure.
With osteoporosis, the microarchitecture of the bone changes. Compared with healthy bone (a), the density of mineral matter decreases, and bone beams thin out (b). © CC BY-SA 3.0. Some rights reserved by Gtirouflet
It is important that the remodeling process goes in a balanced way: how much is "eaten", so much should be accumulated. But when the rate of destruction of bone tissues exceeds the rate of their renewal, osteoporosis will begin to develop.
Osteoporosis is a disease of the skeleton associated with a violation of metabolic processes, which leads to a decrease in bone strength and, as a consequence, to pathological fractures. Such fractures are called low-energy, because the bone breaks already with very little mechanical action on it, which does not happen in a healthy person.
For many years, it was believed that osteoporosis was a far–fetched problem, but statistics indicate that this disease is deadly. Many elderly people are not afraid of a hip fracture for nothing: a fifth of patients with such a diagnosis die a year after the injury, a third of patients receive a permanent disability, and the vast majority have problems with self-care (Cooper, 1997). The numbers are scary…
"Silent" disease
The human skeleton makes up about 15-20% of its body weight, but this value can vary significantly during life. There is a concept of peak bone mass – this is our "safety margin", more specifically, the mass of calcified bone tissue that a person accumulates in youth and carries through life, gradually losing to old age. In women, this "peak" occurs in 20-25 years, in men – five years later. Then the decrease in bone mass begins: in men – smooth, in women – critically sharp, starting with menopause.
The skeletal tissues are constantly undergoing the process of bone remodeling, which involves three types of cells: osteoblasts (young), osteocytes (mature) and osteoclasts-"destroyers". Obsolete osteocytes undergo apoptosis (self-destruction) and are absorbed by osteoclasts. Osteoblasts produce, mainly from collagen, a bone matrix – an osteoid that is "cemented" with calcium phosphate. Osteoblasts immersed in a solid skeleton turn into osteocytes that are unable to divide
There are primary and secondary osteoporosis, which develops against the background of other diseases, such as diabetes mellitus, obesity, rheumatoid arthritis, etc. The main risk factors for the development of the most common primary osteoporosis are old age and menopause in women. Female sex hormones estrogens inhibit the function of osteoclasts, which, with a decrease in the hormonal function of the ovaries, "eat" the bone faster than it has time to recover.
Risk factors for primary osteoporosis also include long-term treatment with glucocorticoid hormones, alcohol abuse, smoking and poor nutrition. Separately, it is worth noting the genetic predisposition, for example, the presence of osteoporosis in the mother, as well as race. It turned out that women of white and yellow races are more prone to osteoporosis compared to Negroid.
The danger of compression fractures of the spine is that at the same time there is a rupture of bone tissue, which initially may not manifest itself in any way. On the right: a typical compression fracture of a vertebra in a patient with osteoporosis, the shape of the vertebra has changed according to the type of wedge-shaped deformation, it has become flattened. Radiograph (NIIKEL SB RAS, Novosibirsk). Left: osteoporosis of the spine. © CC BY 2.0. Some rights reserved by Donut Crash
The danger of all metabolic diseases, and osteoporosis in this sense is no exception, is in the absence of a vivid clinical picture. Unlike infectious diseases, visible signs that make it possible to suspect osteoporosis appear only after a long time has passed since the beginning of the pathological process. The most terrible of them (they are also the main clinical manifestations of the disease) are fractures of the vertebrae and tubular bones of the skeleton, including the so infamous fracture of the femoral neck.
Osteoporosis can also be diagnosed by less obvious signs, such as irreversible changes in posture, back and lower back pain, night cramps in the lower extremities. The vertebral column can be represented in the form of children's cubes stacked on top of each other-vertebrae separated by layers of cartilage tissue. With the rarefaction of bone tissue and spontaneous deformation of the vertebrae, their height decreases. Accordingly, the growth of a person decreases, therefore, with a "shortening" of more than 2.5 cm per year, you need to sound the alarm and start treatment without additional research.
The diagnosis of "osteoporosis" can be made using the usual affordable and cheap radiography of the spine, but only if there are already fractures of the vertebrae. Whereas the main task of treating osteoporosis is to prevent fractures themselves.
When growing up, a person gains his personal peak mass of calcified bone tissue, which he will carry through his whole life, gradually losing to old age. Women reach the peak of this mass earlier than men, and the latter have a much smoother trend of its decline. In women, this decline is critically sharp, which is associated with age-related weakening of ovarian function. © 1999–2018, Rice University. CC BY 4.0
X–ray or ultrasound skeletal densitometry, a method for determining bone mineral density (the amount of mineralized bone tissue in the scanned area), allows to make a diagnosis in the early stages of the disease. This examination is recommended for all women over 50 years of age and men over 70 years of age, but if necessary, it should be done at an earlier age (ISCD, 2007).
And again a healthy lifestyle
Can we influence the process of accumulation-loss of bone mass? Genetic and hormonal factors are practically impossible to control and correct, unlike the other two – nutrition and physical activity.
As for the diet, in short, it should contain the necessary doses of calcium and vitamin D. According to WHO recommendations, an adult should consume at least 1-1.2 g of calcium per day, and in a certain ratio with phosphorus (1: 1.5). The equivalent of a preventive dose of calcium is two glasses of milk a day, but there is a lot of it in other dairy products, especially cheeses, as well as in seeds, nuts, leafy greens, etc.
They say that consuming a lot of calcium is harmful, it contributes to the formation of kidney stones, leads to joint problems. Is that true? And how is it better to take calcium: in the form of medications or with food?
You can eat a lot of calcium, but very little of it will be absorbed – the body knows how to protect itself from its excess. It is impossible to unequivocally answer the question about the sources of calcium: if the right amount of this element is not supplied with food, you have to take appropriate medications. But they are not necessary for the prevention of osteoporosis.
Characteristic changes in posture in osteoporosis can be traced from photographs of Elizabeth II, Queen of Great Britain. In a picture taken in New Zealand in 1953 (left), the cervical, lumbar and thoracic spine of a young slender woman are on the same line. And in the photo taken 64 years later (on the right), the osteoporotic change in posture, which serves as one of the first manifestations of this disease, is clearly noticeable. © CC BY 2.0. Some rights reserved by Archives New Zealand and © CC BY 2.0. Some rights reserved by Gareth Fuller/PA Wire
Does the appointment of hormone replacement therapy help to avoid the development of postmenopausal osteoporosis?
Absolutely, yes. Although this direction is not very popular in Russia, as people here are afraid of hormone therapy. This treatment, of course, has the risk of side effects, just like any other.
However, it is not enough just to consume calcium. It is known that osteoporosis can progress even while maintaining the level of calcium in the blood within the normal range due to a deficiency of vitamins of group D and phosphorus, which prevents its binding in bone tissue. Vitamins D 3 (synthesized in the skin under the action of ultraviolet rays) and D 2 (comes with food) promote the absorption of calcium from the small intestine. According to some reports, in Russia, including Siberia, the population has a deficiency of this vitamin due to the peculiarities of the flow of incident solar radiation, but it can be compensated by including fish, especially fatty fish, seafood, eggs, etc. In the diet. By the way, these same products contain a lot of phosphorus, and also its there is a lot in dairy products (especially cheeses), meat, as well as in corn, legumes, seeds and broccoli.
Bekhterev's disease affects the young
Recently, the emphasis has been on the fact that medicine should be personalized and, most importantly, predictive, so that doctors have the opportunity to prevent the disease. For example, to prevent the development of secondary osteoporosis in patients with spondyloarthritis.
We are talking about a group of rheumatic diseases characterized by inflammatory processes in the joints of the spine and limbs. The brightest and most severe prognosis is ankylosing spondylitis, or Bekhterev's disease. With this disease, irreversible changes occur in the spine: calcium salts slowly but surely accumulate in it, which leads to loss of mobility. In advanced cases, a person turns into a "question mark".
Bekhterev's disease mainly affects young men (the peak incidence occurs at 18-20 years), and its occurrence in the population is about 0.6—0.8%, which is quite a lot (Gubar, 2012; Briot, 2015; Kilic, 2015). At the same time, the average patient receives an accurate diagnosis only 5-7 years after the appearance of the first symptoms. The fact is that, on the one hand, young people, in principle, are not too willing to seek medical help, getting used to morning stiffness and mild pain syndrome. On the other hand, doctors do not always seek to understand such complaints. Military enlistment offices are a separate problem. Until recently, medicine had little to offer such patients. In addition, there are severe forms that do not respond well even to modern methods of therapy.
Bekhterev's disease is characterized by early and very rapid formation of secondary osteoporosis, and at an early stage of the disease, bone metabolism disorders do not allow you to gain peak bone mass, which increases the risk of fractures. Fortunately, osteoporosis does not develop in all such patients, and now doctors, including at our Research Institute of Clinical and Experimental Lymphology (NIIKEL), are trying to develop predictive algorithms to understand who will have it and who will not.
In general, the usual methods of diagnosing osteoporosis in the case of Bekhterev's disease are not suitable. For example, the densitometric method can create a false impression of the presence of dense bone tissue due to foci of pathological ossification of ligaments. And the patients themselves are often physically unable to lie on their backs during this procedure
The FRAX® tool, developed by WHO to assess the risk of fractures in humans, takes into account clinical risk factors and bone mineral density in the femoral neck. The FRAX algorithm is successfully used in postmenopausal women and men 50 years and older to assess the probability of major osteoporotic fractures for the next 10 years. Above: a computerized version of FRAX
Today, the Novosibirsk Research Institute of Clinical and Experimental Lymphology has an Anti–cytokine Therapy Center, which uses the most modern methods of treating Bekhterev's disease - therapy with monoclonal antibodies to tumor necrosis factor alpha and interleukin 17. These are very effective drugs, although they do not help everyone, and besides, they are expensive, so it is very important to be able to predict the effectiveness of treatment.
By the way, there are also so–called "riskometers" in the world - popular methods for determining the risks of fractures in the future, which are based on filling out questionnaires. An example is the FRAX® project, thanks to which a kind of "calculator" appeared to determine the magnitude of the 10–year risk of major osteoporotic fractures, working on the basis of statistics collected within the reference group in different countries. On the FRAX website, anyone can choose a specific country from the list, fill out a questionnaire and get the appropriate forecast.
Unfortunately, such a prognosis will be adequate only for people over forty who have not yet been treated for osteoporosis. This does not apply to patients with Bekhterev's disease. At NIIKEL, today we are creating a riskometer that will be able to determine the likelihood of developing osteoporosis in such patients. Unlike FRAX, we include genetic markers in diagnostic matrices. Their advantage is that they do not depend on a person's lifestyle, the stage of the disease and the activity of the pathological process.
As the main markers, we chose genes encoding cytokines – small informational peptides that regulate intercellular interactions and ensure the consistency of the immune, endocrine and nervous systems of the body. Among other things, they are involved in the regulation of bone remodeling processes.
Cytokine genes are characterized by functional polymorphism (variability), and the analysis of the frequency of occurrence of certain combinations of gene variants (alleles) makes it possible to personalize the prognosis of the disease. In other words, to predict the probability of a severe course of the disease and the risk of osteoporosis for a particular patient, as well as his sensitivity to various medications. The choice of tactics for the treatment of the disease and methods of prevention of secondary osteoporosis will depend on this.
Work on the riskometer is a matter of many years, our method has not yet become a universally recognized and certified tool. But for "internal use" we are already using it, getting good results. And this is our, albeit small, "brick" in the building of a future victory over this insidious disease
Our bones contain about 18% of the total body protein. It can be considered proven that the risk of developing the disease causes both increased and decreased (especially in young people) consumption of protein foods.
A densitometer for measuring bone mineral density looks like a table. Inside this "table", on which the patient lies down in his clothes, an X-ray tube passes. During the study, a receiving element rides above the patient, which removes the indicators. The dose of X-ray irradiation is so small that no additional protection is required. The whole examination takes a few minutes. Photo of the author
It should be added that the strength of the skeleton obviously depends on a number of other vitamins, micro- and macroelements. For example, the lack of copper and zinc leads to a change in the structures of the musculoskeletal system, and chromium is directly involved in the process of calcium transport to the renewing bone. Therefore, the main "gastronomic" advice is banal: food should be varied and balanced. To achieve this in the case of, for example, a vegetarian diet is quite difficult. Such a diet is especially dangerous in youth, when there is a set of peak bone mass – this is a direct road to osteoporosis in old age. By the way, alcohol consumption in moderation also helps to reduce the risk of osteoporosis (Turner, 2000).
Elderly people, in addition to bone fragility, usually develop muscle weakness (sarcopenia), so the risk of falling is much higher, and such a person falls in a specific way – on his side. This is how the hip neck most often breaks. There is a simple test to determine such a risk: 5 times to get up and sit on a chair without the help of hands. If you spend more than 10 seconds on this, you are at risk. In this case, your life should be arranged in such a way as to minimize the chances of falling: wires should not be placed on the floor, it is better to get rid of thresholds and carpets, etc. For the prevention of fractures, hip protectors, special protective pads, bandages for the lumbar region are created, but they, unfortunately, do not always help.
But food is only one side of the coin. To reduce the risk of osteoporosis, adequate physical activity is vital, which allows not only to form the necessary peak bone mass, but also to reduce the rate of its loss with age. An experiment is also known when a volunteer, a healthy young man of athletic build, spent three months in a supine position. He not only lost 8 kg of muscle mass during this time, but, as densitometric analysis showed, his bones became more fragile (Giangregorio, McCartney, 2006).
However, the modern average child eats a lot of carbohydrates, drinks Pepsi-Cola with a high content of orthophosphoric acid, which promotes the leaching of calcium, sits at the computer a lot and generally moves a little. And this is bearing fruit: bone mass in children and adolescents is lower today than a couple of decades ago. It is not difficult to predict what importance the problem of osteoporosis will acquire in the near future.
What kind of physical activity is best suited for the prevention of osteoporosis? After all, bodybuilding, weight lifting is a risk. Maybe dancing is better?
Doctors are unassuming in this regard and are guided by the thesis that any physical activity is better than its absence. But the most physiological ones are walking, running, swimming.
The X-ray shows hip replacements that were installed in a patient with the last stage of polyarthritis. (NIIKEL SB RAS, Novosibirsk).
There are three main reasons for the current "popularity" of osteoporosis problems. Firstly, it is an increase in the life expectancy of people, as a result of which the Earth's population is rapidly "aging". And since osteoporosis sooner or later develops in everyone, then with age a person's chance of living up to its clinical manifestations increases. Secondly, the development of X-ray diagnostic methods makes it possible to determine the disease at relatively early stages and take measures in advance.
Finally, interest in osteoporosis is also supported by space exploration! In zero gravity, the bone loses strength very quickly, so when astronauts land, they are carried on a stretcher, and then they slowly recover under medical supervision. It is because of this "cosmic" reason that drugs for the treatment of osteoporosis have been classified for many years.
Scientists from the Swiss Federal Institute of Technology and IBM Research (Switzerland, Zurich) have been using supercomputers to simulate human bone structures since 2008. These studies are aimed at helping practitioners involved in the diagnosis and treatment of osteoporosis, so that they can quickly and accurately assess the condition (density and fragility) of bones. Left: simulation based on a real sample of human vertebral bone tissue. © CC BY-ND 2.0 Some rights reserved by IBM Research
Today there are a lot of drugs against osteoporosis, which is no coincidence: treatment of this disease without the use of medications is almost impossible. Some of these drugs affect the processes of bone destruction, i.e. the function of osteoclasts, others – on bone formation, i.e. the function of osteoblasts, and others – on both types of cells. The cost of drugs is also different: from hundreds of rubles for mineral and vitamin supplements to several thousand for bisphosphonates of the third generation, which effectively slow down the process of bone resorption.
Treatment must necessarily be selected by a doctor, taking into account both the individual characteristics of the body and the financial capabilities of the patient. By the way, calcium preparations are used, contrary to popular belief, only for prevention, but not for the treatment of osteoporosis.
And of course, you need to understand that none of the modern medicines can stop the passage of time, but the achievements of modern science and medicine are quite capable of slowing it down for our bones.
Literature
Adler R. A., Bayskobing D. M., Bolognese M. A. Osteoporosis. Diagnostics and treatment. Moscow: GEOTAR-Media, 2015. 288 p.
Bartle R. Osteoporosis. Prevention, diagnosis, treatment. Moscow: GEOTAR-Media, 2012. 287 p.
Borinstein D. Get rid of back pain. Moscow: Ripoll, 2004. 512 p.
Kruglyak L. G. Osteoporosis. A quiet epidemic of the XXI century. Tsentrpoligraf, 2014. 220 p.
Osteoporosis / Edited by O. M. Lesnyak, L. I. Benevolenskaya. M.: GEOTAR-Media, 2009. 272 p.
The article is based on a public lecture delivered by the author in the spring of 2018 in one of the bars of Novosibirsk Akademgorodok (Scientific cafe "Eureka").
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