What is bone demineralization and how does it relate to osteoporosis. How can osteoporosis be diagnosed and treated effectively. What are the risk factors for developing osteoporosis and how can it be prevented.

Understanding Bone Demineralization and Its Relation to Osteoporosis

Bone demineralization is a process where the body loses bone minerals faster than it can replace them. This condition can lead to weakened bones and increase the risk of fractures. But how exactly does bone demineralization relate to osteoporosis?

Osteoporosis is a more severe form of bone demineralization. When bone density drops significantly below what’s considered typical, doctors diagnose osteoporosis. This condition affects a substantial portion of the population, with more than 1 in 3 females and 1 in 5 males over age 50 experiencing osteoporosis.

The Composition of Bones

To understand bone demineralization, it’s crucial to know the composition of bones. Approximately 60% of bone mass consists of minerals like calcium and phosphorous. These minerals provide bones with their strength and hardness. However, the body also utilizes these minerals for various other functions, including:

• Supporting nerve function
• Repairing tissues
• Releasing hormones
• Facilitating blood flow through vessels
• Enabling muscle movement
• Transmitting messages to the brain through nerves

The body constantly removes and replaces minerals from bones as needed. However, when the rate of mineral loss exceeds the rate of replacement, bone demineralization occurs.

Factors Contributing to Bone Demineralization

Several factors can contribute to bone demineralization. Understanding these factors is crucial for prevention and management. What are the primary contributors to bone mineral loss?

• Low levels of physical activity
• Extended periods of bed rest
• Chronic heavy alcohol consumption
• Smoking
• Certain medications (e.g., glucocorticoids, antiepileptic medications, some cancer medications, proton pump inhibitors, selective serotonin reuptake inhibitors)
• A diet low in calcium, vitamin D, and protein
• Low estrogen levels in females after menopause or due to hormone disorders
• Extreme physical activity in females
• Low testosterone levels in males

These factors can disrupt the delicate balance of mineral removal and replacement in bones, leading to demineralization over time.

Diagnosing Bone Demineralization and Osteoporosis

How do doctors determine if a patient has bone demineralization or osteoporosis? The primary method for diagnosis is through bone density tests. The most common and reliable test is dual-energy X-ray absorptiometry (DXA or DEXA).

The DEXA Scan Process

DEXA is a painless test that uses X-rays to examine the structure of bones. During the test, doctors measure bone density and assign a T-score based on the results. But what does this T-score mean?

• A T-score of 0 indicates bone density equal to that of a young, healthy adult
• A negative number suggests lower bone density
• A positive number indicates higher bone density

The T-score is measured in standard deviations (SD), a statistical measurement used to estimate how far from average a score falls.

Interpreting T-Scores

Doctors interpret T-scores as follows:

1. Typical: +1 to -1 SD
2. Low (osteopenia): -1 to -2.5 SD
3. Osteoporosis: below -2.5 SD
4. Severe osteoporosis: below -2.5 SD with one or more bone fractures

The U.S. Preventive Services Task Force recommends screening for females over age 65 and females with risk factors for osteoporosis.

Risk Factors for Osteoporosis Development

Osteoporosis is a common condition, but certain factors can increase an individual’s risk of developing it. Who is at a higher risk of osteoporosis?

• Females
• Older adults (risk increases with age)
• Caucasian and Asian females
• Individuals with a slender bone structure
• Those with a family history of the condition
• People with low calcium intake or vitamin D deficiency
• Physically inactive individuals
• Smokers
• Regular consumers of more than 3 alcoholic drinks per day
• Individuals with chronic inflammatory conditions (e.g., rheumatoid arthritis, celiac disease, chronic obstructive pulmonary disease)
• Those taking certain medications (e.g., cancer drugs, heparin, warfarin)

Understanding these risk factors can help individuals and healthcare providers take proactive measures to prevent or manage osteoporosis effectively.

Preventive Measures for Bone Mineral Density Loss

While some risk factors for osteoporosis are beyond our control, there are several preventive measures that can help maintain bone mineral density. How can individuals potentially prevent bone mineral density loss?

• Consuming foods high in vitamin D and calcium
• Taking supplements if vitamin D or calcium levels are low (consult with a doctor before starting any supplement regimen)
• Engaging in regular weight-bearing exercises
• Avoiding smoking or quitting if currently smoking
• Limiting alcohol consumption
• Minimizing the use of medications that can contribute to bone loss (under medical supervision)

The Importance of Weight-Bearing Exercises

Weight-bearing exercises play a crucial role in maintaining bone density. What types of exercises are most beneficial for bone health?

• Strength training
• Hiking
• Walking
• Jogging
• Dancing

These exercises stimulate bone formation and help maintain bone density over time. It’s important to consult with a healthcare provider before starting any new exercise regimen, especially for individuals with existing bone conditions or other health concerns.

Treatment Options for Osteoporosis

When osteoporosis is diagnosed, various treatment options are available to manage the condition and reduce the risk of fractures. What are the primary treatment approaches for osteoporosis?

Medications

Several medications can help slow bone loss or even promote bone formation. These include:

• Bisphosphonates (e.g., alendronate, risedronate, ibandronate, zoledronic acid)
• Denosumab
• Teriparatide
• Abaloparatide
• Romosozumab
• Selective estrogen receptor modulators (SERMs)
• Hormone therapy (for postmenopausal women)

The choice of medication depends on various factors, including the severity of osteoporosis, age, gender, and overall health status. A healthcare provider can determine the most appropriate medication based on individual circumstances.

Lifestyle Modifications

In addition to medications, lifestyle modifications play a crucial role in managing osteoporosis. These may include:

• Dietary changes to increase calcium and vitamin D intake
• Regular weight-bearing and resistance exercises
• Smoking cessation
• Limiting alcohol consumption
• Fall prevention strategies

These lifestyle changes can complement medical treatments and help improve overall bone health.

The Role of Nutrition in Bone Health

Proper nutrition is essential for maintaining strong bones and preventing bone demineralization. What nutrients are crucial for bone health?

Calcium

Calcium is the primary mineral found in bones. Good dietary sources of calcium include:

• Dairy products (milk, yogurt, cheese)
• Leafy green vegetables (kale, spinach, collard greens)
• Fortified foods (orange juice, cereals)
• Sardines and salmon (with bones)
• Almonds and Brazil nuts

Vitamin D

Vitamin D helps the body absorb calcium effectively. Sources of vitamin D include:

• Sunlight exposure
• Fatty fish (salmon, tuna, mackerel)
• Egg yolks
• Fortified foods (milk, cereals)
• Supplements (under medical supervision)

Other Important Nutrients

While calcium and vitamin D are crucial, other nutrients also play a role in bone health:

• Magnesium
• Vitamin K
• Potassium
• Protein

A balanced diet rich in these nutrients can support overall bone health and help prevent bone demineralization.

The Importance of Early Detection and Management

Early detection and management of bone demineralization and osteoporosis are crucial for maintaining quality of life and preventing fractures. Why is early intervention so important?

• Prevents further bone loss
• Reduces the risk of fractures
• Maintains independence and mobility
• Improves overall quality of life
• Reduces healthcare costs associated with fracture treatment and long-term care

Regular bone density screenings, especially for individuals at higher risk, can help detect bone loss early and allow for timely intervention.

The Role of Healthcare Providers

Healthcare providers play a crucial role in the prevention, diagnosis, and management of bone demineralization and osteoporosis. They can:

• Assess individual risk factors
• Recommend appropriate screening tests
• Develop personalized treatment plans
• Monitor treatment effectiveness
• Provide education on lifestyle modifications and fall prevention

Regular check-ups and open communication with healthcare providers are essential for effective osteoporosis management.

Future Directions in Osteoporosis Research and Treatment

The field of osteoporosis research is continually evolving, with new treatments and diagnostic tools on the horizon. What are some promising areas of research in osteoporosis management?

• Gene therapy to promote bone formation
• Development of new medications with fewer side effects
• Improved diagnostic tools for earlier detection
• Personalized treatment approaches based on genetic profiles
• Novel combination therapies for more effective treatment

These advancements hold the potential to improve osteoporosis prevention, diagnosis, and treatment in the future.

The Importance of Ongoing Research

Continued research in the field of bone health is crucial for several reasons:

• Better understanding of bone biology and the mechanisms of bone loss
• Development of more effective and targeted treatments
• Improvement in diagnostic techniques for earlier detection
• Identification of new risk factors and preventive strategies
• Enhancement of patient outcomes and quality of life

As research progresses, individuals with osteoporosis or those at risk can look forward to improved management options and potentially better outcomes.

Is Bone Demineralization the Same as Osteoporosis?

When you lose bone minerals quicker than you can replace them, it’s called bone demineralization. This can lead to other health conditions, including osteoporosis.

About 60% of your bone mass is made up of minerals like calcium and phosphorous.

These minerals give your bones their strength and hardness. Your body also uses them for other tasks, like supporting your nerves and repairing tissues.

Your body constantly removes and replaces minerals from your bones as it needs them. Bone demineralization is when you lose bone minerals quicker than you can replace them.

Bone demineralization can lead to brittle bones that put you at risk of fracture. Doctors will come to a diagnosis of osteoporosis if your bone density drops significantly below what’s considered typical.

According to experts, osteoporosis affects more than 1 in 3 females and 1 in 5 males over age 50.

Keep reading to learn more about bone demineralization and osteoporosis.

A note on sex and gender

In this article, we use the terms “male” and “female” to refer to someone’s biological sex as determined by their chromosomes.

Was this helpful?

Bone demineralization is the loss of minerals from your bone. Your body stores about 99% of your calcium and 85% of your phosphorous in your bones and then constantly removes these minerals to be used elsewhere in the body.

For example, your body uses calcium for:

• releasing hormones
• moving blood through blood vessels
• moving muscles
• carrying messages to your brain through nerves

Usually, your body replaces these minerals at the same rate it removes them. However, factors like hormone levels and diet can lead to demineralization over time.

Your doctor may tell you that you have osteopenia if your bone density drops below what’s considered typical for a young and healthy adult. If it drops very low, they may tell you that you have osteoporosis.

The mineral balance of your bone is largely determined by your hormone levels and your diet.

Factors that can lead to bone demineralization include:

• low levels of physical activity
• extended periods of bed rest
• chronic heavy alcohol consumption
• smoking
• some medications, such as:
  • glucocorticoids
  • antiepileptic medications
  • some cancer medications
  • proton pump inhibitors
  • selective serotonin reuptake inhibitors
• a diet low in:
  • calcium
  • vitamin D
  • protein
• low estrogen levels in females after menopause
• low estrogen levels in females due to hormone disorders or extreme physical activity
• low testosterone levels in males

Doctors can measure your bone density with a bone density test. The most common way your bone density is measured is with dual-energy X-ray absorptiometry (DXA or DEXA). This painless test uses X-rays to see the structure of your bone.

Doctors assign you a T-score based on the results of your scan. A T-score of 0 means your bone density is equal to that of a young, healthy adult. A negative number means your bone density is lower, whereas a positive number means it’s higher.

Your T-score is measured in standard deviations (SD), which is a statistical measurement used to estimate how far away from average your score falls.

Here’s how doctors interpret your score:

Osteoporosis is very common. People with a higher risk of developing osteoporosis include people who:

• are females
• are older adults, with a risk that increases with age
• are Caucasian and Asian females
• have a slender bone structure
• have a family history of the condition
• have a low calcium intake or don’t get enough vitamin D
• aren’t physically active
• smoke cigarettes
• regularly consume more than 3 alcoholic drinks per day
• have any chronic inflammatory conditions like:
  • rheumatoid arthritis
  • celiac disease
  • chronic obstructive pulmonary disease
• take certain medications like:
  • cancer drugs
  • heparin
  • warfarin

Doctors can measure your bone density with a DEXA scan. The results of the scan can allow your doctor to see if you have a lower-than-typical bone density. DEXA of your hip and spine is generally considered the most reliable way to diagnose osteoporosis.

The U.S. Preventive Services Task Force recommends screening for females over age 65 and females who have risk factors for osteoporosis.

You can potentially prevent bone mineral density loss by taking preventive steps, such as:

• eating foods high in vitamin D and calcium and taking a supplement if your levels are low (but be sure to speak with your doctor before taking any supplements)
• performing regular weight-bearing exercises like:
  • strength training
  • hiking
  • walking
  • jogging
  • dancing
• avoiding smoking, or quitting if you currently smoke (this can be difficult, but a doctor can help create a cessation plan that may work for you)
• limiting your alcohol consumption
• minimizing the use and decreasing the dosage of any steroids you are taking (speak with your doctor about finding the best dosage for you)

If you currently have osteoporosis, your doctor may recommend medications to increase your bone mineral density. Medications like bisphosphonates can slow your rate of bone mineral loss, lead to an increase in bone density, and decrease the risk of fracture.

Learn more about how to prevent osteoporosis.

Bone demineralization is the loss of minerals from your bones that makes them more prone to fracture. If your bone mineral density drops well below what is considered typical, your doctor may diagnose you with osteoporosis.

You can lower your chances of developing osteoporosis by taking preventive steps, such as exercising regularly and eating a balanced diet high in calcium and vitamin D. Your doctor may recommend medications to increase your bone density if you currently have osteoporosis.

Is Bone Demineralization the Same as Osteoporosis?

When you lose bone minerals quicker than you can replace them, it’s called bone demineralization. This can lead to other health conditions, including osteoporosis.

About 60% of your bone mass is made up of minerals like calcium and phosphorous.

These minerals give your bones their strength and hardness. Your body also uses them for other tasks, like supporting your nerves and repairing tissues.

Your body constantly removes and replaces minerals from your bones as it needs them. Bone demineralization is when you lose bone minerals quicker than you can replace them.

Bone demineralization can lead to brittle bones that put you at risk of fracture. Doctors will come to a diagnosis of osteoporosis if your bone density drops significantly below what’s considered typical.

According to experts, osteoporosis affects more than 1 in 3 females and 1 in 5 males over age 50.

Keep reading to learn more about bone demineralization and osteoporosis.

A note on sex and gender

In this article, we use the terms “male” and “female” to refer to someone’s biological sex as determined by their chromosomes.

Was this helpful?

Bone demineralization is the loss of minerals from your bone. Your body stores about 99% of your calcium and 85% of your phosphorous in your bones and then constantly removes these minerals to be used elsewhere in the body.

For example, your body uses calcium for:

• releasing hormones
• moving blood through blood vessels
• moving muscles
• carrying messages to your brain through nerves

Usually, your body replaces these minerals at the same rate it removes them. However, factors like hormone levels and diet can lead to demineralization over time.

Your doctor may tell you that you have osteopenia if your bone density drops below what’s considered typical for a young and healthy adult. If it drops very low, they may tell you that you have osteoporosis.

The mineral balance of your bone is largely determined by your hormone levels and your diet.

Factors that can lead to bone demineralization include:

• low levels of physical activity
• extended periods of bed rest
• chronic heavy alcohol consumption
• smoking
• some medications, such as:
  • glucocorticoids
  • antiepileptic medications
  • some cancer medications
  • proton pump inhibitors
  • selective serotonin reuptake inhibitors
• a diet low in:
  • calcium
  • vitamin D
  • protein
• low estrogen levels in females after menopause
• low estrogen levels in females due to hormone disorders or extreme physical activity
• low testosterone levels in males

Doctors can measure your bone density with a bone density test. The most common way your bone density is measured is with dual-energy X-ray absorptiometry (DXA or DEXA). This painless test uses X-rays to see the structure of your bone.

Doctors assign you a T-score based on the results of your scan. A T-score of 0 means your bone density is equal to that of a young, healthy adult. A negative number means your bone density is lower, whereas a positive number means it’s higher.

Your T-score is measured in standard deviations (SD), which is a statistical measurement used to estimate how far away from average your score falls.

Here’s how doctors interpret your score:

Osteoporosis is very common. People with a higher risk of developing osteoporosis include people who:

• are females
• are older adults, with a risk that increases with age
• are Caucasian and Asian females
• have a slender bone structure
• have a family history of the condition
• have a low calcium intake or don’t get enough vitamin D
• aren’t physically active
• smoke cigarettes
• regularly consume more than 3 alcoholic drinks per day
• have any chronic inflammatory conditions like:
  • rheumatoid arthritis
  • celiac disease
  • chronic obstructive pulmonary disease
• take certain medications like:
  • cancer drugs
  • heparin
  • warfarin

Doctors can measure your bone density with a DEXA scan. The results of the scan can allow your doctor to see if you have a lower-than-typical bone density. DEXA of your hip and spine is generally considered the most reliable way to diagnose osteoporosis.

The U.S. Preventive Services Task Force recommends screening for females over age 65 and females who have risk factors for osteoporosis.

You can potentially prevent bone mineral density loss by taking preventive steps, such as:

• eating foods high in vitamin D and calcium and taking a supplement if your levels are low (but be sure to speak with your doctor before taking any supplements)
• performing regular weight-bearing exercises like:
  • strength training
  • hiking
  • walking
  • jogging
  • dancing
• avoiding smoking, or quitting if you currently smoke (this can be difficult, but a doctor can help create a cessation plan that may work for you)
• limiting your alcohol consumption
• minimizing the use and decreasing the dosage of any steroids you are taking (speak with your doctor about finding the best dosage for you)

If you currently have osteoporosis, your doctor may recommend medications to increase your bone mineral density. Medications like bisphosphonates can slow your rate of bone mineral loss, lead to an increase in bone density, and decrease the risk of fracture.

Learn more about how to prevent osteoporosis.

Bone demineralization is the loss of minerals from your bones that makes them more prone to fracture. If your bone mineral density drops well below what is considered typical, your doctor may diagnose you with osteoporosis.

You can lower your chances of developing osteoporosis by taking preventive steps, such as exercising regularly and eating a balanced diet high in calcium and vitamin D. Your doctor may recommend medications to increase your bone density if you currently have osteoporosis.

Benefits of using demineralized xenogenic bone grafts

Benefits of using demineralized xenogenic bone grafts

Keywords: bone grafts, demineralized bone matrix, xenogenic graft.

Treatment of gunshot wounds of extremities, complications and their consequences remain one of the urgent problems of surgery. This is due to the fact that limb injuries make up a fairly high percentage of gunshot wounds, and most of them are accompanied by fractures and bone defects. Currently, the issue of filling bone defects in gunshot wounds, inflammatory and destructive diseases, postoperative (when removing neoplasms) defects and other destructions of long tubular bones remains open. not always the bone tissue is fully restored on its own, or there is no optimal rate of bone restoration without outside intervention. The complexity of these pathologies lies in the polymorphism of pathological conditions leading to the appearance of defects in long tubular bones and in a limited number of treatment methods capable of restoring the damaged bone in a short time with sufficient quality. Compression-distraction osteosynthesis, auto- and allotransplantation, the use of various synthetic implants and osteogenesis stimulators cannot fully solve this problem. All of the above, as well as the ever-increasing number of patients with such a pathology, determine the need to improve the methods used and develop new methods of healing damaged long bones with significant defects. A decrease or insufficiency of the body’s own potential for osteogenesis under conditions of reparative regeneration with extensive bone defects prompts us to look for ways of additional prolonged stimulation of osteosynthesis during the entire period of reparation. Therefore, the solution to the problem of healing damaged long bones with significant defects is possible with the use of implants that have sufficient stimulating activity, induce osteogenesis and resorb during the time required to complete reparative regeneration with the formation of a structurally and functionally complete bone. Literature data indicate the availability of materials that sufficiently meet the requirements for use as grafts, each of which has its own positive and negative sides.

There are five main areas of bone cavity plasty: autoplasty, alloplasty, xenoplasty, implantation and the use of combined grafts (tissues and non-biological substrates). The requirements for the material for local optimization of reparative osteogenesis are high osteogenic potency, lack of antigenicity, ease of preparation, a geometric shape convenient for clinical use, constant availability, economic profitability [2–5,12,37,39].

There are four main mechanisms of influence on the processes of bone regeneration.

1. Osteoblastic osteogenesis stimulated by transplantation of determined osteogenic prodromal cells with the potential for bone formation. This mechanism is known in connection with transplantation of autologous cancellous bone.
2. Osteoconductive osteogenesis develops when allogeneic bone grafts or synthetic bone substitutes are transplanted, which act as a framework for the germination of blood vessels, while cells grow from the bone bed due to the activation of their own determined osteogenic cells. As a result, the allogeneic graft is resorbed and gradually replaced by new bone (calcium hydroxylapatite).
3. Osteoinductive osteogenesis occurs through the phenotypic transformation of non-specific inducible osteoprodromal cells under the influence of humoral factors, in particular bone morphogenetic protein (demineralized bone matrix).
4. Stimulated osteogenesis (osteostimulation) is the effect of certain factors that enhance the already ongoing processes of osteogenesis, that is, stimulate them (for example, a growth factor). A large number of substances of a hormonal nature are known that regulate metabolic and regenerative processes in bone and other tissues [1]. In particular, bone tissue contains bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-J3), epidermal growth factor (platelet derived growth factor (PDGF), insulin-like growth factors I and II (insulin-like growth factor I and II – IGF-I and IGF-II), basic and acidic fibroblast growth factors (basic and acidic fibroblast growth factor – bFGF and aFGF) [34]. Despite the fact that there are relatively few growth factors, they, complexing with cytoplasmic receptors of target cells, activate intracellular enzymes, a multistage (cascade) system, the end product of which can be several biologically active compounds that regulate intra- and extracellular metabolism [1]. All of the above growth factors, except for some morphogenetic proteins, change cell metabolism, and only BMP-2, BMP-3, BMP-4, BMP-6, BMP-7 (OP-1) change the differentiation pathway of various pluripotent mesenchymal cell lines into osteoblastic [ 18. 19.43].

Thus, the local application of various growth factors affects the proliferation, differentiation and synthesis of protein structures in osteoblast cultures and bone formation in various animal models, including experimental fractures and bone defects [35]. Currently, growth factors are commercially available and used in some countries in clinical practice; however, their small amount in bone tissue, the difficulty of isolation and purification, the impossibility of genetically engineered synthesis of some of them (for example, BMPs, due to the unclear chemical structure), and therefore the exceptional high cost, make the use of these factors practically inaccessible in experimental and clinical traumatology and orthopedics.

The use of demineralized bone matrix (DCM) as a plastic material for replacement of human skeletal defects has been going on for several decades. For the first time, demineralized bone, obtained as a step in the preparation of bone for transplantation, was used by Senn in 1889 in an experiment on dogs. The use of DKM began with Urist M.R., who in 1965. systematized (methods of obtaining, processing, conservation), described and experimentally applied the technique of DCM transplantation. Research in this area was carried out in several main areas: material procurement [17,22,24,26,30,31,37, 39, 42], sterilization and conservation [2–5,10,12, 20,25], osteoinduction [11,13,16,20,29,37].

DKM in various forms finds practical application in many areas of surgical treatment of damaged bones. In dentistry, maxillofacial surgery, otolaryngology, traumatology, and neurosurgery, various forms of demineralized or partially demineralized allograft are used [32]. Such an extensive scope of this material is due to a set of unique properties of the demineralized matrix.

In DCM, the osteogenesis control mechanism combines osteoinduction and osteoconduction [36,39]. Osteoinduction is caused by protein substances (bone morphogenetic protein – BMP) located in the extracellular space of the bone tissue. An analysis of the results of other studies in this area shows that the protein consists of several subunits (according to various sources, 4 or 5). Only one of its components, which is a hydrophobic glycoprotein, has morphogenetic properties [40]. Biological activity is exhibited to the maximum extent by the acid-soluble form of CMB [11]. The more acid-soluble form of BMP in the bone, the higher its osteoinductive activity. During demineralization, a significant part of the acid-soluble form of CMB is lost. Based on this, it can be concluded that the osteoinductivity of DCM is largely affected by the time spent in acid [11,40], as well as the type of acid used. In a number of studies Savelyeva V.I. and Khlebovich N.V. (1993) it was noted that DCM obtained by bone demineralization with phosphoric acid exhibited higher osteoinductive properties than DCM after bone demineralization with hydrochloric and hydrobromic acids. On the other hand, bone demineralization in solutions of sulfuric, nitric, nitrous, and chromic acids led to a complete loss of the osteoinductive properties of implants [13,37,41].

If there is a certain commonality of views among most researchers on the problem of choosing acids that are optimal for demineralization, then there is no such unity regarding the degree of demineralization of the bone that is being prepared for use as an implant. Bone demineralization can be carried out by achieving varying degrees of removal of the mineral phase from native bone. According to V.I. Saveliev (1983), demineralization is divided into complete (total), partial (surface) and segmental (selective). The latter was proposed by V.I. Savelyev to obtain implants with predetermined strength properties. Studies by Kakiuchi and Opo (1987) showed that superficially demineralized bone was superior to fully demineralized bone during heterotopic implantation, and no difference was observed with orthotopic implantation. Mundy et al. (1978) suggest that the presence of minerals is necessary to stimulate the resorption process, however, the experiments of other authors [24,28,30] indicate a significantly higher rate of resorption of completely demineralized implants, which, apparently, demonstrates the presence of a mineral residue in the so-called fully demineralized bone . In the studies of Singholm G. et al. (1993) noted that fully demineralized DCM is much more effective than partially demineralized one in the model of rabbit radius defect healing. DKM as a plastic material has a set of important qualities: relative ease of preparation, ease of processing, the possibility of preservation in various ways, and storage time. Of particular interest to specialists is the ability of DCM to provide osteogenesis not only in the bone bed, but also during subcutaneous and intramuscular transplantation, which is explained by the presence of osteoinductive properties in DCM [15,31,37]. At 1965g. Urist M.R. in the experiment showed that non-demineralized bone has a slight osteoinductive effect, compared with demineralized. Demineralization, according to many researchers, contributes to the manifestation of osteoinductivity in the DCM [22,31,37].

The German Central Tissue Bank produces fully human DCM [42], and in the USA (Pacific Coast Tissue Bank – Los Angeles) – superficially demineralized cortical bone [24]. In the experimental and clinical studies of V.I. Savelyev (1983-1996) different depths of bone demineralization are used, depending on the specific clinical application or type of experimental study. Obviously, this approach is the most acceptable, but requires further detailed development.

Immature bone tissue of newborn animals, like fetal bone, contains a large number of growth factors (in particular, TGF-p, FGF and BMPs – [21,23]) and has a similar structure and biochemical composition. Considering this, as well as the limited availability of fetal allograft, native immature bone tissue of newborn animals (for example, immature bone tissue of newborn pigs) can be a source of material for stimulating reparative bone regeneration. At the same time, the use of immature bone tissue of newborn animals (in a demineralized form), according to the literature, was noted in isolated cases, only in experiments to assess the osteoinductivity of DCM from donors of different ages or in native form, in comparison with fetal bone tissue [27] . The stimulating effect of immature bone tissue of newborn animals is apparently associated with the presence of growth factors in its composition in an amount comparable to that of fetal bone tissue, with relatively easy resorption (faster than that of allo). At the same time, the limited amount of available literature data on this type of implantable material determines the need for experimental evaluation of its effect on the reparative regeneration of damaged long bones with significant defects.

In this regard, it is advisable to conduct experimental studies aimed at studying the effect of fragmented native immature demineralized bone tissue of newborn pigs with a specific shape and method of its installation on the reparative regeneration of damaged long bones with significant defects.

Currently on the international market there is a certain list of ready-made drugs from xenogenic bone tissue, which are obtained as a result of a rather complex, laborious and expensive processing, for example, Bio-Oss, Bio-Guide, etc. offered by Geistlich Pharma, Switzerland , which have a fairly high cost in our market. The DKKT offered by us compares favorably and is not inferior to other grafts in its osteogenic properties. The positive qualities of this type of transplants include:

1. Availability of primary material (raw materials), because the graft we offer is obtained from the tubular and flat bones of pigs.
2. Availability of the method of obtaining: DKKT is obtained as a result of conventional demineralization in solutions of inorganic acids according to the method proposed by V.I. Saveliev.
3. Economic benefit of obtaining – from the above it is clear that both primary raw materials and reagents are available and cheap material.
4. The high osteoinductivity of the drug has been proven on the example of already deeply studied allogeneic demineralized bone tissue, as well as experimental material (the active principle is the same morphogenetic protein).
5. Low antigenicity – because when harvesting the drug, newborn piglets are used, the tissues of which have a rather low antigenicity for humans, which is more reduced when treated with hydrochloric acid.
6. Possibility of intraoperative modeling of a transplant of a certain required shape.
7. Heterotopic osteogenesis – there is an increase in bone tissue during heterotopic transplantation.
8. Ease of processing – there is no need to observe strict antiseptic conditions when collecting material, because then it is processed in a hydrochloric acid solution, and preserved in a formalin solution.
9. There is no risk of transmission of infection from the donor to the recipient, due to the strong antiseptic properties of hydrochloric acid and subsequent preservation in formalin.

In conclusion, we consider it necessary to add that the availability and low cost recommend the use of this type of transplant when it is difficult to purchase expensive drugs.
From the foregoing, it is clear that the advantages of this type of graft recommend it for widespread use in the clinic. Of course, it is impossible to achieve the effectiveness of the use of autologous bone grafts, but demineralized xenogenic bone grafts are a worthy substitute for other types of grafts with fairly high osteogenic properties.

Literature

1. Balabolkin M.I. Endocrinology. M. 1998, p. 581.
2. Saveliev V.I. Demineralized bone as a special kind of bone-plastic material. Procurement and transplantation of demineralized bone tissue in experiment and clinic. L., 1983, p. 3.
3. Saveliev V.I. Procurement and preservation of demineralized bone grafts. Method. recommendations. L., 1984, p. 14.
4. Saveliev V.I. Experience in the procurement and use of demineralized bone grafts. Transplantation, demineralization of bone tissue in the pathology of the musculoskeletal system. L., 1990, p. 4.
5. Saveliev V.I., Andrianov V.L., Rumyantsev V.V. and others. Some aspects of procurement and use of demineralized bone grafts. Injuries and diseases of the musculoskeletal system. L., 1982, p. 71.
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Treatment options for bone metastases

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Bone metastases often appear in the last stage of cancer. In countries with a low level of medicine, such patients are often put an end to and go to symptomatic treatment. But in Germany, bone metastases are successfully treated with remote irradiation, radionuclide therapy, ablation, high-intensity focused ultrasound, and other methods. Booking Health specialists tell how bone metastases are treated abroad and what methods are used in developed countries.

Contents

1. What types of cancers metastasize to the bones
2. Consequences of bone metastases
3. Surgery
4. Ablation
5. Radiotherapy of bone metastases

90 018 HIFU therapy

6. Medical therapy
7. Radionuclide therapy
8. Life expectancy of patients with bone metastases

What types of cancer metastasize to the bones

Approximately one third of all distant metastases are found in the bones. In terms of the frequency of involvement in the tumor process, bone tissue ranks third: more often metastases appear only in the lungs and liver.

Bone metastasis can occur in all cancers. However, the vast majority of them are associated with three diseases: breast, prostate and lung cancer.

In breast cancer, bone metastases are detected in 75% of stage 4 patients. This tumor ranks first among all malignant neoplasms in terms of the frequency of bone metastasis. In metastatic prostate cancer, the spine is affected in 90% of cases. Malignant neoplasms of the lung give bone metastases in 40% of patients.

In kidney cancer, the frequency of bone metastasis is 33%, and in malignant neoplasms of the thyroid gland – 28%, and in aggressive types of tumors – up to 60%.

Bowel cancer with bone metastases and ovarian cancer with bone metastases are relatively rare. The frequency of bone metastasis in these tumors does not exceed 10%.

Consequences of bone metastases

Bone metastases are of three types:

• Osteoblastic – with bone growth, increase in its density, compression of adjacent structures
• Osteolytic – with destruction of the bone, increasing the likelihood of its fracture
• Mixed – a combination of two options

Main consequences of bone metastasis:

Pain . It torments a person constantly and periodically intensifies.

Bone fractures . Occur due to demineralization of bone tissue.

Spinal cord compression . Occurs when metastases appear in the spine. Early symptoms are back or neck pain. Then there are numbness of the legs, abdomen, weakness in the legs, incontinence of urine and feces.

Increased blood calcium levels . It is released from broken bones. As a result, the following symptoms develop: constipation, muscle pain, drowsiness, thirst, frequent urination. Over time, kidney failure progresses.

Surgery

A single bone metastasis that causes pain and threatens complications can be surgically removed. This is the most effective method of treatment. With complete removal, local recurrence of the tumor is rare.

Bone resection with arthroplasty is the main radical (completely eliminating metastases) surgery for the treatment of metastatic bone lesions. It is widely used in developed countries. German doctors always prefer organ-preserving interventions, avoiding simpler, but lowering the quality of life, mutilation operations.

In case of metastatic lesions of long bones or the pelvis, the surgeon removes a fragment of bone 8 to 25 cm long, along with the tumor. Since a defect is formed in this zone, it is replaced with “artificial bone”. Doctors install endoprostheses made of titanium alloys, which are not rejected by the body, do not cause inflammatory reactions and gradually grow into your own bone, forming a single whole with it. Less commonly, an allograft (donor bone) is used to replace a defect. As a result of such operations, 9In 5% of patients, the pain syndrome in the area of ​​the operation completely disappears, in 85% there is a complete restoration of the function of the operated part of the body.

Other operations:

• Osteoplasty – injection of bone cement to fix the bone
• Osteosynthesis – installation of fixation structures to stabilize the bone, helps prevent fracture vertebra
• Amputation of a limb or disarticulation (removal of a joint) – mutilation operations, which are almost never used for surgical treatment of bone metastases in developed countries They only allow you to maintain the function of the affected body part and avoid fractures. But these operations are combined with other treatments aimed at destroying cancer cells: for example, with radiation therapy, various types of ablation, radionuclide therapy.

  Ablation

  Ablation is a procedure to destroy a pathological focus. Its advantage is minimal invasiveness. Through a puncture in the skin, doctors insert a needle into the center of the tumor, heat it, as a result of which the malignant cells die.

  Radiofrequency ablation is the most commonly used option. Doctors insert a probe into the tumor tissue and destroy it. This is a minimally invasive procedure that does not cause significant injury to the patient. But it is rarely used as the only treatment, as it increases the risk of bone fracture. It is usually combined with osteoplasty, another minimally invasive procedure to strengthen the bone with cement. Perhaps a combination with osteosynthesis.

  Microwave ablation is an advanced technique that can be used to remove larger metastases. It “burns” the surrounding anatomical structures less, since the distribution of heat does not depend on the density, electrical conductivity and other properties of tissues. The procedure takes less time – an average of 5 minutes. Fabrics are heated to a higher temperature. The treatment technique is similar: a probe is inserted into the tissues, which heats the tumor from the center to the periphery. By adjusting the exposure time, doctors can destroy metastases of different sizes.

  Ablation is often combined with surgery. For example, a doctor may remove a piece of bone with a tumor, and then destroy its soft tissue component using a radiofrequency method.

  Choose a specialized clinic and treatment

  Radiation therapy for bone metastases

  Remote irradiation for metastatic bone lesions is used for palliative purposes. The purpose of this treatment method is to relieve pain and improve the patient’s quality of life. The method is more or less effective in almost all patients. 6 months after irradiation, 70% of treated patients still do not have a pronounced pain syndrome, and 35% have no pain at all.

  Additional effects of radiation therapy:

  • Destruction of tumor foci
  • Restraining their growth
  • Restoration of normal bone structure

  Usually a long course of radiotherapy is not required. The entire course dose is given in 5-6 fractions. Thus, the treatment can be completed in 1 week, and the effect of it lasts for several months. Abroad, linear accelerators of the latest generations are used, which direct radiation to the tumor very accurately. They allow you to safely destroy bone metastases in just one session.

  Local radiation therapy to the area of ​​metastasis does not cure cancer. But it creates good conditions for the use of other methods of therapy, primarily systemic ones, which are aimed at achieving control of the tumor process and increasing the patient’s life expectancy.

  HIFU therapy

  HIFU has been approved in Europe for the treatment of bone metastases since 2015. It involves exposure of the bones to high-intensity focused ultrasound. The main advantage of the method is the absence of invasion, since no needle needs to be inserted into the bone. However, HIFU is only used as a second-line treatment, as an alternative to radiotherapy. It is not considered radical: ultrasound only eliminates pain, reduces the metastatic focus and initiates bone repair. Therefore, HIFU must be combined with other therapies, usually systemic, that inhibit the growth of cancer cells.

  The method is not used for metastases in the bones of the skull and spine. It is often used to suppress metastases in the pelvis, ribs, sternum, shoulder girdle.

  Benefits of HIFU therapy:

  • No radiation
  • No limit on the number of treatments
  • Used for any bone disease: osteoblastic or osteolytic
  • It does not matter if the patient has previously received radiation therapy

  9025 3 Compatible with any other methods and can carried out against the background of chemotherapy

  According to some studies, the effectiveness of HIFU therapy in relieving pain reaches 100%. The effect develops within 3 days. It persists for more than 3 months, and this time is enough to achieve control of the tumor process with the help of medications or other methods of treatment.

  Medical therapy

  Not only local but also systemic treatment is important for the treatment of patients with bone metastases. It is used primarily for the general control of the tumor process. The drugs used suppress cancer cells in all organs and parts of the body at once. Abroad, doctors use not only chemotherapy for bone metastases, but also hormonal, targeted, immune therapy.

  But systemic therapy does not work immediately. Until a therapeutic result is achieved, complications may develop, for example, bone fractures. To prevent complications, bone strengthening with osteomodifying agents is required. These drugs include:

  • Bisphosphonates
  • RANK Ligand Inhibitors (monoclonal antibodies)

  These drugs are prescribed immediately after diagnosis of bone metastases, regardless of whether the patient has symptoms.

  Bisphosphonates have been used in medical practice for over 50 years. This class of drugs inhibits the resorption (resorption) of bone tissue. They reduce pain, improve bone mineralization, and reduce the risk of fractures. In the 21st century, 3rd generation bisphosphonates are being used. They have a more selective effect on bone metastases, additionally cause self-destruction of cancer cells and block the growth of tumor vessels.

  New drugs include RANK ligand blockers. RANK ligand is the main mediator (mediator) in the vicious circle of bone destruction in patients with their metastatic lesion. Monoclonal antibodies block this substance and thereby interrupt the progression of bone tissue destruction. They also inhibit the growth of metastases.

  The effect of taking these drugs:

  • Delayed the first bone event by more than 8 months
  • Reduced the risk of bone events by 17%
  • Delayed pain progression by 2 months
  • Lower risk of switching from NSAIDs to narcotic analgesics
  • Reduction risk of new bone metastases

  Benefits of RANK-ligand inhibitors over bisphosphonates:

  • Do not damage the kidneys
  • Do not accumulate in bones
  • Good treatment tolerance (low toxicity)
  • Convenient administration: one subcutaneous injection every 4 weeks

  Efficacy is equally high in patients with a history of bone events and in those who have not yet suffered complications. Select a specialized clinic and treatment radiation. This is a systemic version of radiation therapy. Its advantage: it acts immediately on all bone metastases.

  Radionuclide therapy has been used since the 1980s. However, initial attempts caused a significant number of complications, primarily from the bone marrow. The radiation penetrated the bone, destroyed the hematopoietic function and suppressed the production of blood cells. The result was severe anemia, bleeding and immunodeficiency.

  In the last 20 years, radiopharmaceuticals have become more gentle and effective. They provide:

  • Selective accumulation in metastatic foci
  • Rapid clearance from healthy tissues
  • High radiation energy to quickly destroy metastases
  • Minimum particle path length to avoid damage to the bone marrow

  Radium-233 is often used in prostate cancer with metastases in Germany. It attacks bone metastases with short alpha radiation that spreads only 0.1 mm. It does not penetrate into the tubular bones and does not have a pronounced effect on the bone marrow.

  There are many other radionuclides that are used to suppress metastases: 153Sm, 89Sr, 32P, 186Re, 188Re, 117mSn, 177Lu.

  Life expectancy of patients with bone metastases

  The prognosis for patients with bone metastases differs, depending on the aggressiveness of the cancer, the presence of other metastases and the quality of treatment.

  For breast cancer with bone metastases, combination therapy usually produces good results. Doctors act not only on metastatic foci, but also treat the disease with systemic methods. They use chemotherapy, hormonal, targeted, immune therapy. Therefore, in developed countries, even after the detection of bone metastases, the three-year survival rate of patients reaches 51.7%, the five-year survival rate is 31.4% (Z. Wang et al.). Moreover, these data were obtained on patients who were treated from 2011 to 2016. Since then, much has changed for the better, new methods of treatment have appeared. Medical oncology is evolving and the outcomes of patients who start therapy today will be much better.

  Doctors get good results in the surgical treatment of metastases in the pelvic bones. The overall five-year survival rate for such patients is 33% (R. Tillman et al., 2019). Only 10% of them need a second operation.

  In lung cancer with bone metastases, the prognosis is worse, but even in these patients, good results can be achieved with quality treatment. In this category of patients, chemotherapy alone is often used. But in this case, the median survival is only 6 months. If the doctors managed to surgically remove the primary tumor and all metastatic foci, then the five-year survival rate of such patients reaches 10-25%, depending on the number and location of metastases. The best prognosis is achieved in patients in whom the tumor has not spread to the pleura.

  Modern methods of treating bone metastases help to reduce pain, prevent fractures, improve quality of life and create conditions for further systemic cancer therapy.