Management of patients with bone metastases and pain syndrome

• What problems do bone metastases lead to?
• How long do people live with bone metastases?
• How are bone metastases diagnosed?
• Modern methods of treatment
• Antitumor drugs for bone metastases
• Radiopharmaceuticals
• Bisphosphonates
• Radiation therapy
• Radiofrequency ablation
• Application of bone cement
• Surgical interventions for bone metastases

Bones are the third most common site of metastases in various cancers, second only to the liver and lungs.

Typically, the appearance of bone metastases indicates that the cancer is in an advanced stage. Radical treatment in such a situation is usually impossible; therapy is palliative.

Most often, prostate and breast cancer metastasize to the bones.

Secondary bone cancer is much more common than primary tumors, especially in adults. Bones and red bone marrow have a good blood supply, so they are easily penetrated by cancer cells present in the bloodstream.

What problems do bone metastases lead to?

Bone metastases lead to excruciating pain and impaired mobility in the joints. Pathological fractures occur due to weakening of bone tissue. Most often in such patients the femur is broken; pathological fractures of the ribs and vertebrae are very common.

Many malignant tumors metastasize to the vertebrae. At the same time, I am bothered by severe chronic pain in the spine, which intensifies and prevents me from sleeping at night. A serious complication may occur - compression of the spinal cord.

Due to the destruction of bone tissue, a large amount of calcium enters the blood, and hypercalcemia develops. It leads to constipation, an increase in the amount of urine, the patient constantly experiences thirst and fatigue. In severe cases, cardiac arrhythmias and renal failure develop.

Proper treatment helps to cope with these symptoms and complications, improve the patient's condition, slow down tumor growth and prolong life.

Risk factors

1. Injury. But there is an opinion that trauma is a common occurrence in children and adolescents and is not a fully proven cause of the development of sarcoma or one of its triggers.
2. Children's age and heavy physical activity. Sarcoma is most often localized in the distal femur and proximal tibia. These are areas of bone tissue growth.
3. Exposure to ionizing radiation. This may be due to radiotherapy for malignant tumors of other locations or living in a radiation zone.
4. The presence of benign tumors prone to malignancy. These are Paget's disease, chondromas, fibrous dystrophy and others.

How long do people live with bone metastases?

The prognosis largely depends on the organ in which the primary tumor is located and its histological type. Median survival for prostate cancer with bone metastases from the moment of diagnosis is 12–53 months (depending on the grade of malignancy), for breast cancer — 19–25 months, for thyroid cancer — 48 months, for renal carcinoma — 12 months , for bladder cancer - 6-9 months, for lung cancer - 6-7 months, for melanoma - 6 months.

Hypercalcemia greatly worsens the prognosis; in such patients, median survival is reduced to 10–12 weeks.

Which parts of the skeleton are most often affected?

The localization of bone metastases is determined not by the nosological affiliation of the primary malignant tumor, but by the functional load and the associated development of the blood supply. Multiple foci in the skeleton are more typical for highly aggressive cancer, single and especially one metastasis indicates a favorable prognosis of the disease.

• Most often, secondary cancer screenings occur in the spongy bones, the vertebrae, which are abundantly fed with blood, and mainly in the lumbar and thoracic spine, which are under high load.
• Next in frequency are metastases in the pelvic bones - almost half of all cases, typical locations are the ilium and pubic bones.
• Metastasis is half as common in the bones of the skull and lower extremity, where damage to the femur predominates.
• The chest, mainly the ribs and sternum, are involved in the malignant process in almost 30% of cases.

How are bone metastases diagnosed?

In some cases, bone metastases can be detected by radiography. In the photographs, the affected areas appear as dark spots, “holes.” But in the initial stages, X-rays are not very informative. Sometimes bone metastases are detected using computed tomography.

The most informative diagnostic method is PET scanning. During the study, a radiopharmaceutical is injected into the patient's body, which accumulates in the tumor tissue and makes it visible in pictures taken using a special device. This helps to identify even small lesions, but sometimes bone infections, arthritis and previous fractures can be mistaken for cancer.

MRI is useful in identifying compression of the nerves and spinal cord.

Blood tests for calcium and alkaline phosphatase levels cannot be the basis for diagnosing bone metastases; they are used in a comprehensive examination, in combination with the above methods. Laboratory tests help identify a complication of bone metastases—hypercalcemia.

Metastasis to the skeleton is one of the most common types of progression of malignant tumors. Bone metastases occur in 70% of patients with cancer of the breast, prostate and thyroid glands, in 30-40% of patients with malignant neoplasms of the lungs, bladder, and less often in patients with kidney cancer, melanoma, and gastrointestinal tumors.

The incidence of bone metastasis [1]: breast - 65-75%, prostate - 65-75%, thyroid - 60%, lung - 30-40%, bladder - 40%, melanoma - 14-45%, kidney - 20-25%.

It is metastatic lesions of the skeleton that cause most cases of cancer pain [2, 3]. Pain syndrome, spinal cord compression, pathological fractures, neurological disorders, hypercalcemia lead to a deterioration in the quality of life of patients against the background of an increase in its duration, associated primarily with significant progress in drug therapy for disseminated processes. All this makes the problem of treating bone metastases invariably relevant and requires further research on this topic.

Mechanisms of bone metastasis and pain syndrome formation

Metastasis is a consequence of a chain of events, including tumor progression in the primary site, the vascularization phase, separation, circulation in the vascular bed, fixation at the site of metastasis, resistance to immune defense, tumor growth at the site of new fixation [4]. The growth of disseminated tumor cells occurs after they enter the bone marrow, where they stimulate local bone cell activity. Antagonism between tumor cells and native bone and bone marrow cells disrupts normal bone homeostasis, leading to tumor growth. Metastatic tumor cells have the ability to initiate mechanisms that stimulate bone resorption, bone formation, or both. The classification of metastatic bone lesions, either osteolytic or osteoblastic, reflects the predominance of one of these mechanisms. The end result is complete bone destruction, which can have severe consequences for the patient [5].

The formation of osteolytic bone metastases is caused by the release of osteoclastogenic agents by tumor cells in the bone microenvironment, while osteoblastic metastases result from the release of factors that stimulate osteoblast proliferation, differentiation, and subsequently uncontrolled bone formation by metastatic tumor cells. However, exclusively lytic or sclerotic bone lesions are the two extremes of the spectrum of activity that leads to tumor destruction of bone, and both of these processes are usually observed in bones affected by metastases [6–8].

The process of bone tissue remodeling is regulated by a number of local and systemic factors. The main point of application is the resorption process carried out by osteoclasts. Control of osteoclast differentiation and function occurs through transcription factor receptor activator kappa B (RANK), its ligand (RANKL), and osteoprotegerin (OPG). RANKL binds to the RANK receptor located on the surface of monocytes, in the presence of macrophage colony-stimulating factor (M-CSF), the fusion of several monocytes occurs with the further formation of a multinucleated osteoclast. Initially, inactive osteoclasts are formed, which are then activated through the interaction of several bone microenvironmental factors, including RANKL and OPG [9].

The main possible pathophysiological mechanisms of pain in patients with bone metastases are the release of chemical mediators, increased pressure inside the bone, microfractures, stretching of the periosteum, reactive muscle spasm, infiltration of nerve roots or their compression by destroyed vertebrae. Bone resorption due to increased osteoclast activity reduces bone density and disrupts bone structure, either in specific areas or in the skeleton as a whole. Microfractures that occur in bone beams in the area of ​​metastasis lead to bone deformation. Stretching of the periosteum due to tumor growth, mechanical pressure on weakened bone, nerve entrapment by a tumor or directly destroyed bone with subsequent collapse are factors associated with the development of bone pain [10]. Cancerous bone pain is a complex condition that occurs through the activation, and ultimately destruction, of primary afferent fibers within the bone. This process can be stimulated directly by prostaglandins, various growth factors, nitric oxide, ATP and other mediators secreted by tumor cells [11].

Radiation therapy in the treatment of metastatic skeletal lesions

Treatment of metastatic skeletal lesions is a complex of medicinal, radiotherapeutic, surgical and interventional methods. The choice of treatment tactics should be made individually, taking into account the characteristics of bone metastases in a given patient and the overall picture of disease progression.

Radiation therapy continues to play an important role in the treatment of skeletal metastases [12–15]. Various options are used - external, systemic radiation therapy, as well as their combination. Traditionally, irradiation for bone metastases was considered a purely palliative method. Modern methods of radiation therapy make it possible to implement treatment programs close to radical in the case of solitary and oligometastases.

The goal of radiation therapy is to reduce pain, prevent a pathological fracture, prevent or reduce neurological symptoms, i.e., improve the patient’s quality of life. In addition, irradiation provides local control of metastatic foci in the skeleton.

The effectiveness of radiation therapy in relation to pain is quite high. The frequency of general analgesic effect is 60–90% [16].

The mechanism of the analgesic effect of radiation therapy for bone metastases is not completely clear. The late analgesic effect may be partly a consequence of tumor cell death, as well as the direct effect of irradiation on osteoclast formation through its effect on the proliferation of progenitor cells [17]. There is an opinion that the early analgesic effect of radiation therapy may be associated with inhibition of prostaglandin E2 produced by inflammatory cells in tumor tissue [18]. The analgesic effect of radiation therapy is associated with changes in nociceptive transmission in the central nervous system. Experimental studies in animals have shown that radiation can reduce pain by altering pain-related signals in the spinal cord. Proteins implicated in radiation-induced analgesia are likely to be secretagogin, syntenin, P2X6, and CaM kinase 1. Their putative function is to participate in the control of vesicular transport, ATP-mediated fast synaptic transmission, and the calcium signaling cascade [19, 20].

Efficacy of external beam radiation therapy for bone metastases

Standard options for external beam radiation therapy involve the use of the following radiation regimens: 8 Gy once, 20 Gy in 5 fractions, 24 Gy in 6 fractions, 30 Gy in 10 fractions.

In a review by M. Popovic et al. [21] presented international patterns of use of palliative radiotherapy in the treatment of symptomatic bone metastases from 1993 to 2013—21 studies out of 301 MEDLINE and EMBASE search results. According to the analysis, the lowest dose prescribed by radiation oncologists was 3 Gy in 1 fraction, the highest was 60 Gy in 30 fractions, and the most commonly used regimen was 30 Gy in 10 fractions. Using ANOVA analysis of variance, the authors identified various parameters influencing the choice of radiotherapy technique, in particular the preference for the use of single versus fractionated radiation. Statistically significant prognostic factors were the location of metastases in the skeleton and their number, the location of the primary tumor, the presence of spinal cord compression, as well as demographic parameters (geographical location of the hospital, treatment in a university or private clinic).

According to numerous studies, the effectiveness of single and fractionated irradiation is generally comparable. However, the need for repeated radiation therapy associated with relapse of pain syndrome is significantly higher with a single irradiation (Table 1).

Table 1. Efficacy of single and fractionated irradiation of skeletal metastases

The purpose of a multicenter randomized study by the International Atomic Energy Agency was to determine the optimal dose of a single irradiation of bone metastases with pain [27]. In the period from 2008 to 2012, 651 patients were examined and randomized into two groups: a single radiation dose of 8 Gy was administered to 325 patients and 4 Gy to 326 patients. The intensity of pain was assessed using categorical and visual analogue scales. The volume of irradiation for metastases in the spine included one vertebra above and below the affected ones. For other localizations of metastases, as well as in the presence of a soft tissue component, they retreated 2 cm from the affected area. The authors did not reveal statistically significant differences in the effectiveness of radiation therapy depending on demographic indicators, simultaneous drug therapy (chemotherapy, hormone therapy, bisphosphonate therapy), and initial pain intensity. The overall effectiveness of radiation and the likelihood of complete pain relief were significantly higher in the group with a dose of 8 Gy. There was a lower rate of re-irradiation in the 8 Gy group (45 cases) compared to the 4 Gy group (72 cases), which also turned out to be statistically significant.

C. Rutter et al. [28] studied the frequency of use of single-dose irradiation and found that it differs significantly not only in different countries, but also in clinics within the same country. According to the authors, the choice of a single or fractionated irradiation technique is not always associated only with medical indications. Other factors may also be important, in particular the patient’s distance from the clinic, whether he has health insurance that covers the costs of treatment for cancer.

According to the ASTRO Evidence-Based Guideline [29], a single dose of 8 Gy radiation is associated with a higher risk of pain recurrence compared with fractionated radiation. Evidence regarding the higher risk of pathological fractures remains equivocal. The technique of a single irradiation dose of 8 Gy provides a good overall analgesic effect, does not cause severe radiation damage that would limit its use, and can be recommended for patients with a short life expectancy.

In other cases, preference should be given to fractionated radiation therapy.

Review by R. Chow et al. [30] is devoted to the issue of choosing the optimal dose for fractionated irradiation. 17 randomized studies containing data on the overall, partial and complete analgesic effect were selected for analysis. 7 fractionation modes were analyzed: 20 Gy in 2 fractions, 20 Gy in 5 fractions, 20 Gy in 10 fractions, 22.5 Gy in 5 fractions, 24 Gy in 6 fractions, 30 Gy in 10 fractions and 30 Gy in 15 fractions. Most researchers used 4- and 5-point pain rating scales, as well as a visual analogue scale. The frequency of the general analgesic effect was greatest for the 22.5 Gy/5 regimen - 92%; for the 20 Gy/10, 30 Gy/15 and 30 Gy/10 regimens it was 78, 76 and 75%, respectively. The 22.5 Gy/5 regimen also demonstrated the highest complete pain relief rate at 42%, which was virtually identical to the 30 Gy/15 regimen at 41%. The lowest percentage of complete analgesic effect was observed for the 20 Gy/5 (27%) and 30 Gy/10 (21%) regimens. The re-irradiation rate was highest for the 20 Gy/5 regimen and amounted to 16%. This was followed by a regimen of 30 Gy/10 - 11% and 24 Gy/6 - 7%. In addition, the highest incidence of spinal cord compression, 6%, has been described when using 20 Gy/5. The 20 Gy/5 and 30 Gy/10 regimens demonstrated the highest incidence of pathological fractures at 5%. Based on these data, it seems that the effectiveness of the 20 Gy/5 regimen is lower. However, the review authors believe that, given the small differences in efficacy rates, it can be concluded that there is no significant difference in pain relief for skeletal metastases between the radiation regimens used in these studies. A similar conclusion was made regarding the toxicity of all irradiation options.

Stereotactic radiotherapy for skeletal metastases

Stereotactic radiotherapy (SBRT) for the treatment of bone metastases has been introduced to the treatment of spinal lesions, allowing for high dose delivery to the tumor while minimizing exposure to surrounding tissue.

According to the recommendations of the ASTRO Evidence-Based Guideline [29], stereotactic radiation therapy for spinal metastases should be carried out in the case of spinal or paraspinal metastases visualized on MRI, with damage to no more than 2 consecutive or 3 non-adjacent spinal segments, in patients over 18 years of age, with Karnofsky index 40-50 or more, in inoperable patients or in case of refusal of surgical treatment, in the presence of residual tumor after surgery, with a histologically confirmed diagnosis of a malignant neoplasm, biopsy of a newly detected metastasis, in the case of oligometastases or only bone metastases. For re-irradiation, the dose of previous conformal radiation therapy should not exceed 45 Gy.

The effectiveness of SBRT, according to various studies, is quite high. The frequency of general analgesic effect is 80-90%. A number of authors describe the probability of complete pain relief exceeding 50%. The level of local control is 85-90% (Table 2).

Table 2. Efficacy of stereotactic radiation therapy for skeletal metastases Note. OE—general effectiveness, PE—full effect, LC—local control.

Recently, stereotactic radiation therapy has been used not only to treat spinal metastases, but also for other localizations of metastatic foci in the skeleton. In the work of D. Erler et al. [39] presented the results of treatment of 106 patients with non-spinal metastases. Median follow-up was 13 months (0.25–45.6). The majority of patients (60.5%) are men. The most common primary tumor was prostate cancer (32%). In most cases, metastases were localized in the pelvic bones (41.5%), more than half were osteoblastic. In most cases, regimens of 30 and 35 Gy in 5 fractions were used. Relapse rate 13.3%. It was found that the likelihood of relapse was significantly related to PTV. The larger the volume of the lesion, the more often relapses develop. Pathological fractures in the irradiation zone were registered in 8.5% of cases, on average after 8.4 months; they were more often observed in lytic metastases and in female patients. The authors conclude that SBRT in the treatment of non-spinal metastases provides a high level of local control with a low risk of pathological fractures.

Radionuclide therapy in the treatment of skeletal metastases

In recent decades, radionuclide therapy has been actively used to treat patients with skeletal metastases. Indications for the use of this method are multiple lesions without the threat of pathological fracture, resistant to systemic drug therapy, visualized by osteoscintigraphy and localized in areas of pain.

Contraindications are the threat of pathological fracture and compression of the spinal cord, planned myelosuppressive therapy, progression of extraosseous metastases, severe general condition of the patient (Karnofsky index less than 60, life expectancy less than 2 months), any acute conditions, exacerbation of chronic diseases, as well as hematological contraindications.

The goal of radionuclide therapy is to suppress pain, as well as have an antitumor effect on bone metastases, inhibit the progression of the disease and, as a result, improve the quality and increase the life expectancy of patients.

To treat metastases in the skeleton, radiopharmaceuticals based on 153Sm, 89Sr, 32P, 33P, 186Re, 188Re, 117mSn, 177Lu, 90Y,131I, etc. are used. Radionuclide therapy is effective in 60-80% of cases with a probability of complete pain relief of 15-35%. The best results can be achieved in the treatment of bone metastases of breast and prostate cancer [40–44] (Table 3).

Table 3. Efficacy of systemic radiation therapy for skeletal metastases

In recent years, the effectiveness of radiopharmaceuticals based on alpha emitters and primarily 223Ra-dichloride in bone metastases of prostate cancer has been actively studied. Thus, the results of the widely publicized ALSYMPCA study indicate not only a significant reduction in the risk of bone complications and the need for subsequent use of external beam radiation therapy in the group receiving radionuclide therapy compared with placebo, but also a significant increase in the median overall survival of patients with castration-resistant metastatic prostate cancer from 11 ,6 to 16 months [50, 51]. The results of the use of 223Ra in breast cancer look less encouraging, however, even here, in some cases, it was possible to achieve a stable analgesic effect [52, 53]. In this regard, the data on the possible effectiveness of 223Ra in osteolytic metastases and the supposed effect on dormant tumor cells look interesting, but still rather speculative [54].

Active searches for compounds that increase the targeting of radionuclides continue. Among them are radiopharmaceuticals (including theranostic pairs) based on bisphosphonates, cathepsin K inhibitors and other compounds [55]. Among the compounds that have already found use in clinical practice, mention should be made first of all of the radioligands of the prostate-specific membrane antigen: 131I-MIP-1095 and 177Lu-PSMA. The main task of these radiopharmaceuticals is not so much the relief of bone pain syndrome, but rather the effect on all tumor foci and, accordingly, an increase in survival rate in disseminated, usually hormone-refractory prostate cancer. Nevertheless, along the way, stable pain relief is achieved with therapy with these radioligands in 35–84% of cases [56–58].

Summarizing the data obtained to date, it should be noted that significant progress in medical and surgical treatment methods in oncology has not yet led to a reduction in the need for radiation treatment of bone metastases. Moreover, the development of radiation therapy technologies expands the indications for its use, primarily towards a noticeably greater “radicality” in the case of oligometastatic lesions. At the same time, the most important task on the path to its improvement remains the search for optimal dose-volume ratios during remote irradiation of metastases of various nature, location and structure. In turn, expanding the range of effective radionuclides and searching for new tumor-tropic carriers (or combinations thereof) are the central points of increasing the effectiveness of targeted radioligand therapy.

It can be assumed that the combination of a high degree of individualization of targeted radionuclide therapy based on theranostic pairs and the universalism of “nonspecific” high-dose precision external irradiation may turn out to be one of the most promising directions for the development of not only radiation therapy for bone metastases, but also radiation therapy in general.

The authors declare
no conflict of interest.
The authors declare no conflict of interest.

Information about authors

Bychkova N.M. — https://orcid.org/0000-0002-5177-2612, e-mail;

Khmelevsky E.V. — https://orcid.org/0000-0002-4880-0213, e-mail

Corresponding author:

Bychkova N.M. — e-mail: [email protected]

Bychkova N.M., Khmelevsky E.V. Modern approaches to radiation therapy of metastatic skeletal lesions. Oncology. Journal named after P.A. Herzen

. 2019;8(4):295-302. https://doi.org/10.17116/onkolog20198041295

Modern methods of treatment

Many patients diagnosed with bone metastases become discouraged and stop treatment, believing that nothing more can be done. Despite the fact that remission is usually impossible, the patient can still be helped. There are different types of treatment available that help:

• slow down the growth of secondary lesions;
• cope with symptoms;
• improve general condition and increase life expectancy.

When drawing up a treatment program, the doctor takes into account the symptoms, location and characteristics of the primary tumor, the location and number of bone metastases, the presence of complications in the form of pathological fractures and hypercalcemia.

Antitumor drugs for bone metastases

When prescribing antitumor therapy, the doctor primarily focuses on the primary tumor. Bone metastases are made up of cells characteristic of the organ from which the cancer has spread. In different cases, certain types of drugs will be effective:

• Chemotherapy drugs are administered intravenously or taken orally. Treatment is carried out in cycles. After administering the drugs, the body is given a “break”, then the cycle is repeated. The course of treatment consists of several cycles.
• Hormonal drugs are effective for hormone-positive tumors, primarily prostate and breast cancer. In breast cancer, tumor growth can be stimulated by estrogens, in prostate cancer - androgens.
• Targeted drugs block certain molecules that promote the growth and survival of cancer cells and the formation of new blood vessels. In order to correctly prescribe targeted therapy, the doctor must know the molecular genetic characteristics of the tumor in a particular patient.
• Immunotherapy drugs use the immune system's resources to destroy cancer cells. Currently, a modern class of immunotherapy drugs—checkpoint inhibitors—is being successfully used.

Treatment is continued as long as the tumor responds to it and no serious side effects occur. If the prescribed drugs stop working, the doctor selects another combination.

Cause

So, a very common cause of bone pain is metastatic cancer. That is, the doctor and the patient are no longer faced with primary, but with secondary oncology. Atypical cells of a primary disease of any organ can damage bone and cause pain.

Moreover, it is the bones that are most susceptible to metastasis of atypical cells into them, which often penetrate there with the bloodstream, attaching to the vascular wall of the network of capillaries located in the bone tissue.

Another way (this happens much less frequently) of penetration of atypical cells into the bone is ingrowth from a tumor localized in the immediate vicinity.

The cause of pain is the disruption of the normal functioning of bone cells by cancer cells. This changes the structure of bone tissue.

When a bone is healthy, it constantly undergoes the process of destruction of old tissue and the formation of new one. Once in the bone, atypical cells disrupt this balance. The attacked periosteum (bone membrane) and nerves react to the invasion, causing pain.

Radiopharmaceuticals

Radiopharmaceuticals are radioactive substances that, after intravenous administration, reach tumor tissue, accumulate in it and destroy cancer cells. This is an alternative to traditional radiation therapy. If a patient has multiple metastases, it is not advisable to irradiate every bone: this is not very effective and can cause serious side effects. It is worth giving preference to radiopharmaceuticals: they spread through the bloodstream throughout the body and reach all secondary foci.

Currently, in foreign literature there is data on the successful use of strontium-89 (Metastron), samarium-153 (Quadramet), radium-223 (Xofigo). Radiopharmaceuticals have been shown to be effective in reducing pain in affected bones for several months. If necessary, the procedure can be repeated.

Radiopharmaceuticals work best for osteoblastic metastases, when the activity of osteoblasts, the cells that form new bone tissue, is increased.

Why does pain occur?

Pain is caused by three reasons:

1. destruction of the richly innervated periosteum by a cancerous conglomerate;
2. irritation of pain receptors in the periosteum by biologically active waste products of cancer cells;
3. involvement of muscle nerve endings in the metastatic node.

Unbearable pain is not always associated with skeletal metastasis; as a rule, this is a consequence of the high aggressiveness of tumor cells in the terminal stage of the process, when the concentration of biologically active substances in the blood is enormous - cytokines, which literally “burn” the nerve endings of even tissues not affected by the tumor. With a high degree of malignancy of the primary tumor, pain is observed more often and more intensely. The most obvious example is widespread and persistent pain in completely intact bones due to lung adenocarcinoma; surgery to remove the affected lung completely cures the pain.

Bisphosphonates

Bisphosphonates are drugs that inhibit the activity of osteoclasts, cells that break down bone tissue. They help cope with pain, strengthen bones, prevent pathological fractures, and reduce calcium levels in the blood. However, bisphosphonates should be used with caution because they can cause serious complications, including severe renal impairment and osteonecrosis of the jaw.

A safer alternative is denosumab - this drug also suppresses osteoclast activity, but its mechanism of action differs from bisphosphonates.

How do OMAs act on bone?

The “point of application” for any bisphosphonate is the bone destroyer osteoclast. Direct destruction of bone is carried out not by tumor cells, but by osteoclasts activated by waste products of the tumor. The bisphosphonate is deposited in the bone matrix; during osteolysis - bone destruction, it is released into the surrounding tissues, creating very high concentrations, and has a devastating effect on osteoclasts.

The main pharmacological effect of all bisphosphonates is to suppress the activity of osteoclasts, limiting their numbers by inhibiting their formation from progenitor cells and, ultimately, triggering apoptosis - programmed cell death.

Osteoblasts also provide “call signs” for the activation of osteoclasts. By acting on osteoblasts, bisphosphonates also inhibit the synthesis of osteoclast-stimulating factors. It is on this link that the monoclonal antibody denosumab acts precisely, preventing osteoblasts from producing a substance that stimulates the maturation and activation of osteoclasts.

Bisphosphonates also have a direct cytotoxic effect on tumor cells, reducing the attachment of tumor cells to bone tissue and invasion—their penetration deep into the bone. There are also other, less important ways to prevent bone resorption. Thus, all bisphosphonates, regardless of generation, stop pathological bone resorption, the manifestations of which are bone complications.

Radiation therapy

Radiation helps relieve bone pain and prevent pathological fractures. Treatment is carried out in one of two modes:

• You can carry out 1-2 procedures, during which large doses of radiation are given to the bone. This is convenient for the patient, as the number of trips to the clinic is reduced.
• Another scheme involves 5-10 sessions in smaller doses. In this case, the total dose will be slightly higher than in the first case; in such patients, pain is less likely to recur and there is a need for re-treatment.

Surgical interventions for bone metastases

Surgeries for bone metastases are palliative in nature. The doctor uses screws, pins, plates, and other structures to strengthen the bone or restore its integrity after a pathological fracture. This helps manage pain and improve the function of the affected body part. If surgery is contraindicated, special splints are used, as for ordinary fractures.

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Metastases - what is it?

This term is quite scary for any person. Indeed, metastases are secondary, often distant, malignant lesions of any tissue in the body. The cancerous tumor itself can be localized in any part of the body, sometimes located very far from the area affected by metastases.

Metastases - what is it?

The presence of metastases significantly complicates the treatment of the underlying cancer, which often turns out to be completely powerless. These abnormal cells quickly and easily spread throughout the body without control. True, this happens only at a certain stage in the course of the underlying pathology.

Metastases to the spine

Metastases can also appear in the spine. Here they often affect the vertebrae themselves and structures close to them. They are usually detected in such parts of the spine as the lumbar, thoracic, and rarely in the cervical. Regarding the human skeleton, this is the most common malignant pathology.

Cancer metastasis

On a note! Most often, this type of secondary formations in the spine is found in lung cancer, malignant neoplasms of the prostate or mammary glands. Their “donors” are the kidneys, lungs, digestive organs, thyroid gland, etc. Metastasis of the spinal region often accompanies myelomas, sarcomas and lymphomas.

Table. Types of metastases in the spine.

Osteoblastic metastases