References

endoserg

Эндокринная хирургия

Endocrine Surgery

2306-35132310-3965

Типография «Печатных дел Мастер»

10.14341/serg201445-14

endoserg-6981

Research Article

Обзоры литературы

Review of literature

Патогенез остеоартропатии Шарко: роль периферической нервной системы

The pathogenesis of Charcot osteoarthropathy: the role of the peripheral nervous system

Галстян

Гагик Радикович

Radikovich

Galstyan Gagik

доктор медицинских наук, заведующий отделением терапевтических и хирургических методов лечения диабетической стопы

MD, PhD, Professor

mariagrishina2006@yandex.ru

Каминарская

Юлия Андреевна

Kaminarskaya

Yuliya Andreevna

osipovaulia@gmail.com

ФГБУ ЭНЦРоссияEndocrinology Research Centre, MoscowRussian Federation

2014

28012015

84514

2014

Галстян Г.Р., Каминарская Ю.А.

Radikovich G.G., Kaminarskaya Y.A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.surg-endojournals.ru/jour/article/view/6981

Нейроостеоартропатия является редким, но тяжелым осложнением периферической нейропатии. Это состояние характеризуется прогрессирующей деструкцией костей и суставов стопы и приводит к необратимой инвалидизации пациентов. На сегодняшний день безусловно лидирующей причиной нейроостеоартропатии является сахарный диабет (СД), преимущественно с поражением стопы и голеностопного сустава. Патогенез до сих остается предметом дискуссий. Последние исследования указывают на ведущую роль системы RANK/RANKL/OPG в развитии данного осложнения. На настоящий момент отсутствуют фармакологические методы терапии с доказанной эффективностью. Со времен Жан-Мартена Шарко, был достигнут лишь небольшой прогресс в лечении. Общепризнанным стандартом лечения на сегодняшний день является полная разгрузка конечности при помощи иммобилизирующей повязки из полимерных материалов. Целью этой обзорной статьи является анализ исследований, проведенных в области патогенеза ОШ, обсуждение возможного дальнейшего развития представления о природе данного состояния. Особое внимание уделено современной концепции, рассматривающее поражение нервной системы в качестве ведущего звена в развитии костной патологии. Выявление новых аспектов патогенеза ОШ способно привести к появлению фармакологических методов лечения этой группы пациентов.

Neuroosteoarthropathy is a rare, but devastating complication affecting patients with peripheral neuropathy. It is a progressive, destructive condition that is characterised by progressive bone and joint deterioration of the foot leading to permanent incapacity. Nowadays, diabetes mellitus is by far the most common etiology of CNO (Charcot neuro-osteoarthropathy), especially if it affects the foot or ankle.

The cause of the condition is still controversial among experts. In particular, new data have emerged on the central role of RANK/RANKL/OPG in the pathogenesis of this complication, also known as Charcot foot. No pharmacological methods of therapy have proven effective to date. Very little progress has been made in treating this condition since the days of Jean-Martin Charcot. Today, the universally accepted treatment involves completely relieving pressure from the limb using a polymer retaining bandage. The aim of this review is to analyze research into the pathogenesis of CNO and our potential to better understand the nature of this condition.

Particular attention is paid to modern concept of neuroosteopathology, according to which neuropathy is crucial to developing acute osseous pathology. Revealing new aspects of CNO pathogenesis can help extend therapeutic resources for treating this patient group.

сахарный диабетстопа Шарконервные волокнанейропептидыпатофизиология

diabetes mellitusCharcot jointnerve fibresneuropeptidesphysiopathology

References1

Petrova NL, Edmonds ME. Charcot neuro-osteoarthropathy-current standards. Diabetes Metab Res Rev 2008;24 Suppl 1:S58–61. doi:10.1002/dmrr.846.

Jones KB, Mollano A V., Morcuende JA, Cooper RR, Saltzman CL. Bone and brain: a review of neural, hormonal, and musculoskeletal connections. Iowa Orthop J 2004;24:123–32.

Rostom S, Bahiri R, Mahfoud-Filali S, Hajjaj-Hassouni N. Neurogenic osteoarthropathy in leprosy. Clin Rheumatol 2007;26:2153–5. doi:10.1007/s10067-007-0629-7.

Mabilleau G, Edmonds ME. Role of neuropathy on fracture healing in Charcot neuro-osteoarthropathy. J Musculoskelet Neuronal Interact 2010;10:84–91.

Larson SAM, Burns PR. The pathogenesis of Charcot neuroarthropathy: current concepts. Diabet Foot Ankle 2012;3. doi:10.3402/dfa.v3i0.12236.

Chisholm KA, Gilchrist JM. The Charcot joint: a modern neurologic perspective. J Clin Neuromuscul Dis 2011;13:1–13. doi:10.1097/CND.0b013e3181c6f55b.

Slater RA, Ramot Y, Buchs A, Rapoport MJ. The diabetic charcot foot. Isr Med Assoc J 2004;6:280–3.

Wukich DK, Sung W. Charcot arthropathy of the foot and ankle: modern concepts and management review. J Diabetes Complications 2009;23:409–26. doi:10.1016/j.jdiacomp.2008.09.004.

Van Baal J, Hubbard R, Game F, Jeffcoate W. Mortality associated with acute Charcot foot and neuropathic foot ulceration. Diabetes Care 2010;33:1086–9. doi:10.2337/dc09-1428.

Armstrong DG, Lavery LA. Elevated peak plantar pressures in patients who have Charcot arthropathy. J Bone Jt Surg - Ser A 1998;80:365–9.

БРЕГОВСКИЙ ВБ, ЦВЕТКОВА ТЛ, ЛЕБЕДЕВ ВВ, КРЮЧКОВА ЗВ, КУЗЬМИНА ВА, КАРПОВА ИА, et al. ОСОБЕННОСТИ БИОМЕХАНИКИ СТОПЫ ПРИ ДИАБЕТИЧЕСКОЙ АРТРОПАТИИ ШАРКО. Сахарный Диабет 2005;1.

Edmonds ME, Clarke MB, Newton S, Barrett J, Watkins PJ. Increased uptake of bone radiopharmaceutical in diabetic neuropathy. Q J Med 1985;57:843–55.

Chantelau E, Onvlee GJ. Charcot foot in diabetes: farewell to the neurotrophic theory. Horm Metab Res 2006;38:361–7. doi:10.1055/s-2006-944525.

Jeffcoate WJ, Game F, Cavanagh PR. The role of proinflammatory cytokines in the cause of neuropathic osteoarthropathy (acute Charcot foot) in diabetes. Lancet 2005;366:2058–61. doi:10.1016/S0140-6736(05)67029-8.

Baumhauer JF, O'Keefe RJ, Schon LC, Pinzur MS. Cytokine-induced osteoclastic bone resorption in charcot arthropathy: An immunohistochemical study. Foot Ankle Int 2006;27:797–800.

Uccioli L, Sinistro A, Almerighi C, Ciaprini C, Cavazza A, Giurato L, et al. Proinflammatory modulation of the surface and cytokine phenotype of monocytes in patients with acute Charcot foot. Diabetes Care 2010;33:350–5. doi:10.2337/dc09-1141.

Petrova NL, Moniz C, Elias DA, Buxton-Thomas M, Bates M, Edmonds ME. Is there a systemic inflammatory response in the acute charcot foot? Diabetes Care 2007;30:997–8. doi:10.2337/dc06-2168.

Jeffcoate W. Vascular calcification and osteolysis in diabetic neuropathy-is RANK-L the missing link? Diabetologia 2004;47:1488–92. doi:10.1007/s00125-004-1477-5.

Hofbauer LC. The Role of Receptor Activator of Nuclear Factor- B Ligand and Osteoprotegerin in the Pathogenesis and Treatment of Metabolic Bone Diseases. J Clin Endocrinol Metab 2000;85:2355–63. doi:10.1210/jc.85.7.2355.

ЯРОСЛАВЦЕВА МВ, УЛЬЯНОВА ИН, ГАЛСТЯН ГР, ИЛЬИН АВ, НИКАНКИНА ЛВ, РЕМИЗОВ ОВ. CОСТОЯНИЕ СИСТЕМЫ ОСТЕОПРОТЕГЕРИН (OPG) - ЛИГАНД РЕЦЕПТОРА-АКТИВАТОРА ЯДЕРНОГО ФАКТОРА КАППА-В (RANKL) У ПАЦИЕНТОВ С ДИАБЕТИЧЕСКОЙ ОСТЕОАРТРОПАТИЕЙ И МЕДИАКАЛЬЦИНОЗОМ АРТЕРИЙ НИЖНИХ КОНЕЧНОСТЕЙ. Остеопороз И Остеопатии 2008;1.

Ndip A, Williams A, Jude EB, Serracino-Inglott F, Richardson S, Smyth J V, et al. The RANKL/RANK/OPG signaling pathway mediates medial arterial calcification in diabetic Charcot neuroarthropathy. Diabetes 2011;60:2187–96. doi:10.2337/db10-1220.

Mabilleau G, Petrova NL, Edmonds ME, Sabokbar A. Increased osteoclastic activity in acute Charcot’s osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand. Diabetologia 2008;51:1035–40. doi:10.1007/s00125-008-0992-1.

Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337–42. doi:10.1038/nature01658.

Jeffcoate WJ, Rasmussen LM, Hofbauer LC, Game FL. Medial arterial calcification in diabetes and its relationship to neuropathy. Diabetologia 2009;52:2478–88. doi:10.1007/s00125-009-1521-6.

Sinha S, Munichoodappa CS, Kozak GP. Neuro-arthropathy (Charcot joints) in diabetes mellitus (clinical study of 101 cases). Medicine (Baltimore) 1972;51:191–210.

Salo P. The role of joint innervation in the pathogenesis of arthritis. Can J Surg 1999;42:91–100.

Craig a AD, Heppelmann B, Schaible HG. The projection of the medial and posterior articular nerves of the cat’s knee to the spinal cord. J Comp Neurol 1988;276:279–88.

Schaible HG, Schmidt RF. Activation of groups III and IV sensory units in medial articular nerve by local mechanical stimulation of knee joint. J Neurophysiol 1983;49:35–44.

Schenk I, Spaethe A, Halata Z. The structure of sensory nerve endings in the knee joint capsule of the dog. Ann Anat 1996;178:515–21.

Li J, Kreicbergs A, Bergström J, Stark A, Ahmed M. Site-specific CGRP innervation coincides with bone formation during fracture healing and modeling: A study in rat angulated tibia. J Orthop Res 2007;25:1204–12. doi:10.1002/jor.20406.

Hukkanen M, Konttinen YT, Santavirta S, Paavolainen P, Gu XH, Terenghi G, et al. Rapid proliferation of calcitonin gene-related peptide-immunoreactive nerves during healing of rat tibial fracture suggests neural involvement in bone growth and remodelling. Neuroscience 1993;54:969–79.

Santavirta S, Konttinen YT, Nordstrom D, Makela A, Sorsa T, Hukkanen M, et al. Immunologic studies of nonunited fractures. Acta Orthop Scand 1992;63:579–86.

Bjurholm A, Kreicbergs A, Brodin E, Schultzberg M. Substance P- and CGRP-immunoreactive nerves in bone. Peptides 1988;9:165–71.

Hill EL, Elde R. Distribution of CGRP-, VIP-, D?H-, SP-, and NPY-immunoreactive nerves in the periosteum of the rat. Cell Tissue Res 1991;264:469–80. doi:10.1007/BF00319037.

Salo PT, Theriault E. Number, distribution and neuropeptide content of rat knee joint afferents. J Anat 1997;190:515–22. doi:10.1017/S0021878296001902.

Offley SC, Guo T-Z, Wei T, Clark JD, Vogel H, Lindsey DP, et al. Capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. J Bone Miner Res 2005;20:257–67. doi:10.1359/JBMR.041108.

Uzan B, de Vernejoul M-C, Cressent M. RAMPs and CRLR expressions in osteoblastic cells after dexamethasone treatment. Biochem Biophys Res Commun 2004;321:802–8. doi:10.1016/j.bbrc.2004.07.037.

Schinke T, Liese S, Priemel M, Haberland M, Schilling AF, Catala-Lehnen P, et al. Decreased bone formation and osteopenia in mice lacking alpha-calcitonin gene-related peptide. J Bone Miner Res 2004;19:2049–56. doi:10.1359/JBMR.040915.

Kawase T, Okuda K, Burns DM. Immature human osteoblastic MG63 cells predominantly express a subtype 1-like CGRP receptor that inactivates extracellular signal response kinase by a cAMP-dependent mechanism. Eur J Pharmacol 2003;470:125–37. doi:10.1016/S0014-2999(03)01763-1.

Vignery A, McCarthy TL. The neuropeptide calcitonin gene-related peptide stimulates insulin-like growth factor I production by primary fetal rat osteoblasts. Bone 1996;18:331–5. doi:10.1016/8756-3282(96)00017-8.

Ballica R, Valentijn K, Khachatryan A, Guerder S, Kapadia S, Gundberg C, et al. Targeted expression of calcitonin gene-related peptide to osteoblasts increases bone density in mice. J Bone Miner Res 1999;14:1067–74. doi:10.1359/jbmr.1999.14.7.1067.

Huebner AK, Schinke T, Priemel M, Schilling S, Schilling AF, Emeson RB, et al. Calcitonin deficiency in mice progressively results in high bone turnover. J Bone Miner Res 2006;21:1924–34. doi:10.1359/jbmr.060820.

Wang L, Shi X, Zhao R, Halloran BP, Clark DJ, Jacobs CR, et al. Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-kappaB activation, osteoclastogenesis and bone resorption. Bone 2010;46:1369–79. doi:10.1016/j.bone.2009.11.029.

Imai S, Matsusue Y. Neuronal regulation of bone metabolism and anabolism: calcitonin gene-related peptide-, substance P-, and tyrosine hydroxylase-containing nerves and the bone. Microsc Res Tech 2002;58:61–9. doi:10.1002/jemt.10119.

Goto T, Nakao K, Gunjigake KK, Kido MA, Kobayashi S, Tanaka T. Substance P stimulates late-stage rat osteoblastic bone formation through neurokinin-1 receptors. Neuropeptides 2007;41:25–31. doi:10.1016/j.npep.2006.11.002.

Wang L, Zhao R, Shi X, Wei T, Halloran BP, Clark DJ, et al. Substance P stimulates bone marrow stromal cell osteogenic activity, osteoclast differentiation, and resorption activity in vitro. Bone 2009;45:309–20. doi:10.1016/j.bone.2009.04.203.

SHERMAN B, CHOLE R. A mechanism for sympathectomy-induced bone resorption in the middle ear. Otolaryngol - Head Neck Surg 1995;113:569–81. doi:10.1016/S0194-5998(95)70048-X.

Matayoshi T, Goto T, Fukuhara E, Takano H, Kobayashi S, Takahashi T. Neuropeptide substance P stimulates the formation of osteoclasts via synovial fibroblastic cells. Biochem Biophys Res Commun 2005;327:756–64. doi:10.1016/j.bbrc.2004.12.055.

Rusanen M, Korkala O, Gronblad M, Partanen S, Nederstrom A. Evolution of substance P immunofluorescent nerves in callus tissue during fracture healing. J Trauma 1987;27:1340–3.

Hukkanen M, Konttinen YT, Rees RG, Santavirta S, Terenghi G, Polak JM. Distribution of nerve endings and sensory neuropeptides in rat synovium, meniscus and bone. Int J Tissue React 1992;14:1–10.

Mukohyama H, Ransjö M, Taniguchi H, Ohyama T, Lerner UH. The inhibitory effects of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide on osteoclast formation are associated with upregulation of osteoprotegerin and downregulation of RANKL and RANK. Biochem Biophys Res Commun 2000;271:158–63. doi:10.1006/bbrc.2000.2599.

Delgado M, Abad C, Martinez C, Leceta J, Gomariz RP. Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nat Med 2001;7:563–8. doi:10.1038/87887.

Pittenger G, Vinik A. Nerve growth factor and diabetic neuropathy. Exp Diabesity Res 2003;4:271–85.

Donaghy M, Hakin RN, Bamford JM, Garner A, Kirkby GR, Noble BA, et al. Hereditary sensory neuropathy with neurotrophic keratitis: Description of an autosomal recessive disorder with a selective reduction of small myelinated nerve fibres and a discussion of the classification of the hereditary sensory neuropathies. Brain 1987;110:563–83.

Lindberger M, Schröder HD, Schultzberg M, Kristensson K, Persson A, Östman J, et al. Nerve fibre studies in skin biopsies in peripheral neuropathies. I. Immunohistochemical analysis of neuropeptides in diabetes mellitus. J Neurol Sci 1989;93:289–96.

Koeck F-X, Bobrik V, Fassold A, Grifka J, Kessler S, Straub RH. Marked loss of sympathetic nerve fibers in chronic Charcot foot of diabetic origin compared to ankle joint osteoarthritis. J Orthop Res 2009;27:736–41. doi:10.1002/jor.20807.

Shakoor N, Agrawal A, Block JA. Reduced lower extremity vibratory perception in osteoarthritis of the knee. Arthritis Rheum 2008;59:117–21. doi:10.1002/art.23241.

La Fontaine J, Harkless LB, Sylvia VL, Carnes D, Heim-Hall J, Jude E. Levels of endothelial nitric oxide synthase and calcitonin gene-related peptide in the Charcot foot: a pilot study. J Foot Ankle Surg 2008;47:424–9. doi:10.1053/j.jfas.2008.05.009.

Borovikova L V, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000;405:458–62. doi:10.1038/35013070.

Van Maanen MA, Lebre MC, van der Poll T, LaRosa GJ, Elbaum D, Vervoordeldonk MJ, et al. Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice. Arthritis Rheum 2009;60:114–22. doi:10.1002/art.24177.

Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 2005;434:514–20. doi:10.1038/nature03398.

Ishizuka K, Hirukawa K, Nakamura H, Togari A. Inhibitory effect of CGRP on osteoclast formation by mouse bone marrow cells treated with isoproterenol. Neurosci Lett 2005;379:47–51. doi:10.1016/j.neulet.2004.12.046.

Amano S, Arai M, Goto S, Togari A. Inhibitory effect of NPY on isoprenaline-induced osteoclastogenesis in mouse bone marrow cells. Biochim Biophys Acta 2007;1770:966–73. doi:10.1016/j.bbagen.2007.02.009.

Aro H, Eerola E, Aho AJ. Development of nonunions in the rat fibula after removal of periosteal neural mechanoreceptors. Clin Orthop Relat Res 1985;NO. 199:292–9.

Dysart PS, Harkness EM, Herbison GP. Growth of the humerus after denervation. An experimental study in the rat. J Anat 1989;167:147–59.

Dietz FR. Effect of peripheral nerve on limb development. J Orthop Res 1987;5:576–85.

SINGER M. The influence of the nerve in regeneration of the amphibian extremity. Q Rev Biol 1952;27:169–200.

Aro H. Effect of nerve injury on fracture healing. Callus formation studied in the rat. Acta Orthop Scand 1985;56:233–7.

Glenn JN, Miner ME, Peltier LF. The treatment of fractures of the femur in patients with head injuries. J Trauma 1973;13:958–61.

McMaster WC, Stauffer ES. The management of long bone fracture in the spinal cord injured patient. Clin Orthop Relat Res 1975;no.112:44–52.

Irie K, Hara-Irie F, Ozawa H, Yajima T. Calcitonin gene-related peptide (CGRP)-containing nerve fibers in bone tissue and their involvement in bone remodeling. Microsc Res Tech 2002;58:85–90. doi:10.1002/jemt.10122.

Richard J-L, Almasri M, Schuldiner S. Treatment of acute Charcot foot with bisphosphonates: a systematic review of the literature. Diabetologia 2012;55:1258–64. doi:10.1007/s00125-012-2507-3.

Zhang Y-B, Wang L, Jia S, Du Z-J, Zhao Y-H, Liu Y-P, et al. Local injection of substance P increases bony formation during mandibular distraction osteogenesis in rats. Br J Oral Maxillofac Surg 2014. doi:10.1016/j.bjoms.2014.07.002.

Ma L, Xiang L, Yao Y, Yuan Q, Li L, Gong P. CGRP-alpha application: a potential treatment to improve osseoperception of endosseous dental implants. Med Hypotheses 2013;81:297–9. doi:10.1016/j.mehy.2013.04.025.

The authors declare that there are no conflicts of interest present.