RU2700497C1 - Method for treating complicated biophosphonate osteomyelitis of jaw bones - Google Patents

Method for treating complicated biophosphonate osteomyelitis of jaw bones Download PDF

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RU2700497C1
RU2700497C1 RU2019112966A RU2019112966A RU2700497C1 RU 2700497 C1 RU2700497 C1 RU 2700497C1 RU 2019112966 A RU2019112966 A RU 2019112966A RU 2019112966 A RU2019112966 A RU 2019112966A RU 2700497 C1 RU2700497 C1 RU 2700497C1
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wound
sorbent
osteomyelitis
cotton
treatment
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RU2019112966A
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Олег Викторович Нестеров
Марианна Маратовна Валиева
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Государственное автономное учреждение здравоохранения "Республиканская клиническая больница Министерства здравоохранения Республики Татарстан"
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Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, particularly to maxillofacial surgery, and can be used for local treatment of purulent wounds. Substance of the method for treating the complicated course of bisphosphonate osteomyelitis of the jaw bones involves using the cotton pulp as a sorbent. Wound biosorption bandage is applied on the entire wound surface of a sorbent produced from cotton powder with fiber length of not less than 10 mcm, which is filled in a purulent wound completely covering it. Ligation is performed by powder addition every 12 hours till the wound is completely cleaned.EFFECT: technical result consists in absence of pain syndrome and postoperative inflammatory edema; excluding the possibility of secondary infection of the wound, reducing the length of the postoperative wound healing and the absence of side and allergic reactions.1 cl, 3 dwg, 1 tbl

Description

The invention relates to medicine, in particular to maxillofacial surgery, and can be used for local treatment of purulent wounds.

Osteonecrosis of the jaw is a serious complication that occurs in patients receiving treatment with bisphosphonates. The incidence of jaw osteonecrosis in patients with malignant tumors receiving therapy ranges from 0.8 to 18.6% [1]. In studies by Brown et al. in 2013, it was found that the incidence of jaw osteonecrosis in patients receiving zoledronic acid therapy after tooth extraction with poor hygiene is significantly higher and amounts to 86.4% [2].

When teeth are removed, or other bone tissue injury occurs, a local release of BP bisphosphonates occurs, which inhibit the proliferation of epithelial cells and disrupt the healing of soft tissues of the maxillofacial region, as a result of which the bone tissue undergoes prolonged contact with the microflora of the oral cavity [3].

A number of studies have shown that bisphosphonates affect both bone cells (osteoclasts, osteocytes, osteoblasts) and macrophages, endothelial cells, monocytes, tumor cells and significantly reduce the level of circulating vascular endothelial growth factor (VEGF), which leads to to inhibition of capillary formation [4].

The American Association of Oral and Maxillofacial Surgeons (2009) has proposed various treatment regimens for patients with jaw osteonecrosis depending on the stage of the process. Treatment includes antiseptic treatment of foci with antibiotic therapy, and in the presence of sequestration, surgical treatment consisting in sequestrectomy [5].

Taking into account all the above, it is possible to draw an obvious conclusion that the development of effective methods for the prevention and treatment of jaw osteonecrosis in patients receiving bisphosphonate therapy is an urgent problem in modern maxillofacial surgery and oncology.

The means used in the local treatment of wounds include a group of medical sorbents that provide an active cleansing effect on the wound. The development of methods for local treatment of wounds with their use has led to the development of a whole area, called sorption-application therapy. Active medical sorbents should have the necessary level of sorption ability, prevent absorption of the wound in the tissue, ensure its outflow, remove microbial bodies and their metabolic products, provide a pronounced anti-inflammatory, necrolytic, analgesic, decongestant effect, create conditions for optimal repair. Of the medical sorbents, our attention was attracted by cellosorb - a water-swelling sorbent based on carboxymethyl cellulose. Choosing it as a prototype predetermined the fact that it has an affinity for dressings and is prepared from cotton cellulose and is quite inexpensive. However, it has a significant drawback - the presence in its composition of a large number of carboxyl groups, which, by binding to the protein components of biological fluids, form a kind of protective barrier on the surface of the sorbent particles that prevents liquid diffusion, which significantly reduces the drainage effect [6].

The purpose of the invention is to improve the treatment results of bisphosphonate osteomyelitis complicated by abscesses and cellulitis of soft tissues by using a sorbent made from cotton cellulose with a fiber length of 50 μm, providing an antimicrobial, analgesic and wound healing effect that can be well fixed on the wound surface.

The invention is expressed by a combination of essential features sufficient to achieve the desired technical result, which consists in improving the results of treatment of biophosphonate osteomyelitis of the jaw bones, and includes: the absence of pain and postoperative inflammatory edema; elimination of the possibility of secondary infection of the wound; reduction in the healing time of the postoperative wound; lack of adverse and allergic reactions.

The essence of the method of treatment of the complicated course of biophosphonate osteomyelitis of the jaw bones involves the use of cotton cellulose as a sorbent. A wound biosorption dressing is applied on the entire surface of the wound from a sorbent obtained from cotton and powder pulp with a fiber length of at least 10 μm, which is poured into a purulent wound, completely covering it. Dressing is carried out by adding powder every 12 hours until the wound is completely cleansed.

The sorbent obtained from cotton and powder cellulose with a fiber length of 50 μm differs from analogues in greater dispersion, which increases the binding capacity of cellulose blood and sweat bandages by 8-9%.

The sorbent from cellulose is cotton, powder, with a fiber length of at least 10 microns, retains its volume and properties on the wound surface for 12 hours.

We have developed an interactive dressing based on the sorbent according to the patent of the Russian Federation No. 2675219, designed to close wound surfaces. To determine the properties of the sorbent necessary for its use as a wound cover, laboratory studies of the level of adhesion, vapor permeability, and drainage properties were carried out.

Cotton cellulose sorbent - a white substance, powdery, soft consistency, hygroscopic, with a fiber size of at least 10 microns.

Wound healing is a complex biological phenomenon in which not only cellular elements of connective tissue are involved, but also numerous factors of the immune system, including cytokines [7]. For an objective assessment of the effectiveness of sorption-application therapy in the treatment of a complicated course, it was decided to use a study of cytokine levels in wound fluid.

Normally, their spectrum is narrow, but under stress, inflammation, damage, tumor formation, etc., the quantitative and qualitative composition of cytokines with both local and distant (hormonal) activity expands. Cytokines are produced by various cells: endotheliocytes, keratinocytes, fibroblasts, macrophages, neutrophils, lymphocytes, platelets, stromal cells [4]. According to Roelofs A.J. et al. (2006), biophosphonates affect both bone cells (osteoclasts, osteoblasts, osteocytes) [8] and macrophages, endothelial cells, monocytes, tumor cells (eg, multiple myeloma cells and prostate cancer) [9] . Impaired cytokine secretion is the main cause leading to the development of a severe inflammatory process and sluggish tissue regeneration.

The object of our study was the wound discharge of 60 patients, who were divided equally into 2 groups - the main (OG) and the comparison group (HS). In patients with OH, the wound surface was covered with a sorbent, in patients with a gauze dressing. The levels of proinflammatory cytokine - tumor necrosis factor (TNFα) and anti-inflammatory cytokine - interleukin-10 (IL-10), as well as transforming growth factor (TGF β-1 ) on the 2nd and 7th days after the operation period were determined in the wound discharge . For the study, the Pro Con FNO-α, Pro Con IL-10 kits (St. Petersburg) were used, and Quintikin (USA) was used to determine β-1 TGF. The results were recorded using a Multiscan spectrophotometer (Germany).

Based on the analysis of indicators of cytokine levels conducted in dynamics, significant differences were found between the parameters of patients with hypertension and HS, the data obtained are summarized in a table.

Figure 00000001

A statistically significant and more pronounced decrease in the level of proinflammatory cytokine TNFα on the 7th day was observed in patients with hypertension (p <0.001), less pronounced in patients with HS (p <0.01). As for the comparison of this parameter, it reliably prevailed in patients with HS (p <0.01).

In turn, on the 7th day there was a statistically significant decrease in the level of anti-inflammatory cytokine IL-10, both in patients with hypertension and HS (p <0.001). Moreover, the level of IL-10 in patients with hypertension was significantly higher than this HS indicator (p <0.05).

Since pro- and anti-inflammatory cytokines are involved in local processes, a decrease in their levels may be due to a gradual decrease in the severity of the inflammatory process itself that occurs in response to damage (surgery) by the 7th day of treatment.

The TGF- β-1 index in the dynamics of the course of the wound process also tended to change, but already upward, more pronounced in patients with GO (p <0.001). When comparing these indicators of both observed groups, higher and statistically significant parameters were observed in patients with hypertension compared with patients with HS. This circumstance indicates an earlier, and more pronounced, activation of repair processes in patients in whose treatment sorption-application therapy was used.

Thus, the use of sorption-application therapy in the treatment of the complicated course of biophosphonate osteomyelitis of the jaw bones in the early stages eliminates the severity of the inflammatory process. The use of a sorbent made of cotton and powder cellulose with a fiber length of at least 10 microns reduces the level of pro - and anti-inflammatory cytokines and increases the level of transforming growth factor TGF β-1 . The observation results in all patients of the main group, in contrast to patients in the comparison group, confirmed that the application of the proposed method reduces the treatment time and contributes to the formation of normotrophic scars.

The method is illustrated in the illustrations, where:

In FIG. 1 shows a photo of the wound surface on the 3rd day after the operation: the wound is filled with fine-grained granulation tissue;

In FIG. 2. - on the 5th day after the operation, scant wound compartment is noted;

In FIG. 3. - on the 7th day after the operation - epithelialization by primary intention.

The method is as follows.

After opening and draining the abscess, revising the fistulous course in the oral cavity, and antibiotic therapy, the patient, in the area of the postoperative wound, is applied a wound biosorption dressing from a sorbent obtained from cotton, powder pulp with a fiber length of at least 10 μm. Sorbent is poured into a purulent wound, completely covering it, dressing is carried out by adding powder every 12 hours until the wound is completely cleansed.

Clinical example.

Patient N., 54 years old. 06/20/2018 was admitted to the Department of Oral and Maxillofacial Surgery, Kazan State Children's Clinical Hospital, Ministry of Health of the Republic of Tajikistan in a planned manner with a diagnosis of Chronic bisphosphonate osteomyelitis of the lower jaw on the right. From the anamnesis: since 2015, suffering from breast cancer with bone metastases in the spine. For the treatment of bone metastases, courses of zollendronic acid 4 mg are administered intravenously once a month. Chemotherapy began in October 2017. A week before the start of chemotherapy, 44, 46, 47 teeth were removed in the dental clinic at the place of residence due to complicated caries. In March 2018, pain appeared in the lower jaw on the right, in the area of missing teeth. The patient underwent complex treatment: necrosecvestrectomy by oral access, in the postoperative period - antibiotic therapy, daily dressings (a 0.05% chlorhexidine solution was used to treat the sutures). The patient was discharged on the 8th day of illness in a satisfactory condition, wound healing in the oral cavity was performed by secondary intention.

On October 31, 2018, the patient re-applied to the GAUZ RKB MH RT with complaints of pain in the lower jaw on the right, painful swelling of the soft tissues in the submandibular region on the right, and suppuration in the oral cavity.

An exacerbation of chronic bisphosphonate osteomyelitis of the lower jaw was diagnosed on the right. Subperiostal abscess of the lower jaw on the right. The treatment was carried out: periostotomy, necrosequestrectomy by extraoral access, revision of the fistulous course in the oral cavity, antibiotic therapy and daily dressings (0.01% miramistin solution was used for suture treatment). The patient was discharged on the 15th day of the disease in satisfactory condition, wound healing in the oral cavity was performed by secondary intention.

On January 25, 2019, the patient turned to the GAUZ RKB MH RT for the third time with complaints of pain in the lower jaw on the right, painful swelling of soft tissues in the submandibular region on the right, suppuration in the oral cavity and fistulous passage in the submandibular region on the right.

An exacerbation of the process with a pathological fracture of the lower jaw was diagnosed. In this area, a postoperative scar with fistulous passage, the presence of purulent discharge is visualized.

The treatment was performed: opening and draining the abscess, necrosecvestrerectomy, osteosynthesis of the lower jaw by extraoral access, revision of the fistulous course in the oral cavity, antibacterial therapy. Daily dressings with powdered, cotton cellulose, with a fiber length of at least 10 microns, were performed by the patient by adding, from the date of admission, every 12 hours. The patient was discharged on the 11th day of the disease in satisfactory condition, wound healing took place without complications.

After 5 days from the start of the use of the sorbent, a decrease in hyperemia and tissue edema was noted. The edges of the wounds were reduced, necrotic tissue was torn away, the wound surface was filled with granulations.

Thus, clinical trials of powdered, cotton cellulose have shown that the new sorbent is a relatively inexpensive biocompatible material. Unlike a large number of other sorbents, it has a sufficient level of not only sorption, but also drainage ability, pronounced bactericidal, anti-inflammatory, analgesic, decongestant, and wound healing effects, and creates optimal conditions for active reparative processes in the wound, which allows to achieve a favorable course of postoperative period at earlier dates.

Information sources:

1. Kyrgidis, A. Bisphosphonaterelated osteonecrosis of the jaws: a case-control study of risk factors in breast cancer patients [Text] / A. Kyrgidis, K. Vahtsevanos, G. Koloutsos [et al.] // J. Clin. Oncol. - 2008 .-- # 26, - P. 4634-4648.

2. Brown J, Saad F, Stopeck A, et al. Risk factors for developing osteonecrosis of the jaw (ONJ) in patients receiving denosumab or zoledronic acid for bone metastases: Results from three phase 3 trials. The European Cancer Congress 2013, Sep 30. Abstract 1305.

3. Andous, B.H. The effectiveness of ozone against microorganisms on test surfaces [Text] / V.N. Andous // Ecological and epidemiological surveillance of natural focal infections in the Northern Caspian: sb. scientific work. - Astrakhan, 1996 .-- S. 154.

4. Zimina I.V., Lopukhin Yu.M., Arion V.Ya. Skin as an immune organ: cellular elements and cytokines // Immunology. - 1994. - No. 1. - S. 8-13.

5. Ruggiero, S.L. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws - 2009 update [Text] / S.L. Ruggiero, T.B. Dodson, L.A. Assael, [et al.] // J. Oral Maxillofac. Surg. - 2009 .-- N67, Suppl. 5. - P. 2-12.

6. Kondratiev, VB, Bone metastases: complicated forms, hypercalcemia, spinal cord compression syndrome, drug treatment [Text] / VB Kondratiev, V.V. Martynyuk, L.A. Lee // Practical Oncology. - 2000. - No. 2. - S. 41-45.

7. Babaeva A.G. Regeneration and immunogenesis system. - M.: Medicine. -1985. - 256 s.

8. Maruotti, N. Bisphosphonates: effects on osteoblast [Text] / N. Maruotti, A. Corrado, A. Neve, F.P. Cantatore // Eur. J. Clin. Pharmacol - 2012. - Vol. 68, No. 7. - P. 1013-1018.

9. Coxon, F.P. Protein synthesis is required for caspase activation and induction of apoptosis by bisphosphonate drugs [Text] / F.P. Coxon, H.L. Benford, R.G.G. Russel, M.J. Rogers // Mol. Pharmacol - 1998. - No. 54. - P. 631-638.

Claims (1)

  1. A method of treating the complicated course of biophosphonate osteomyelitis of the jaw bones, comprising using cotton cellulose as a sorbent, characterized in that a wound biosorption dressing is applied from the sorbent obtained from cotton powder pulp with a fiber length of at least 10 μm to the purulent wound over the entire surface of the wound. completely covering it, dressing is carried out by adding powder every 12 hours until the wound is completely cleansed.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU667068B2 (en) * 1991-12-10 1996-03-07 Acordis Speciality Fibres Limited Cellulosic fibres
EP0766756B1 (en) * 1994-06-22 1998-09-02 Courtaulds Fibres (Holdings) Limited Process for the manufacture of lyocell fibre
RU2480191C2 (en) * 2006-08-04 2013-04-27 ЭсТиБи ЛАЙФСЭЙВИНГ ТЕКНОЛОДЖИЗ, ИНК. Hard bandage for treatment of injured tissue
US20130152309A1 (en) * 2001-09-12 2013-06-20 Convatec Technologies Inc. Antibacterial wound dressing
RU2675219C1 (en) * 2018-06-26 2018-12-17 Вячеслав Александрович Лашков Method of manufacturing cellulose surgical cotton

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU667068B2 (en) * 1991-12-10 1996-03-07 Acordis Speciality Fibres Limited Cellulosic fibres
EP0766756B1 (en) * 1994-06-22 1998-09-02 Courtaulds Fibres (Holdings) Limited Process for the manufacture of lyocell fibre
US20130152309A1 (en) * 2001-09-12 2013-06-20 Convatec Technologies Inc. Antibacterial wound dressing
RU2480191C2 (en) * 2006-08-04 2013-04-27 ЭсТиБи ЛАЙФСЭЙВИНГ ТЕКНОЛОДЖИЗ, ИНК. Hard bandage for treatment of injured tissue
RU2675219C1 (en) * 2018-06-26 2018-12-17 Вячеслав Александрович Лашков Method of manufacturing cellulose surgical cotton

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