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Broken bone muscle spasm. Muscle-Bone Interactions in Fracture Healing: A Comprehensive Guide

by alexxlab

How do muscles and bones interact during fracture healing. What are the key stages of fracture repair. How does blood supply affect bone healing. What role do pericytes play in bone regeneration. How can muscle flaps influence fracture recovery. What factors can lead to delayed union or non-union of fractures.

The Biological Process of Fracture Healing

Fracture healing is a complex biological process that involves the intricate interplay between various tissues, cells, and signaling molecules. Understanding this process is crucial for healthcare professionals and researchers working in the field of orthopedics and traumatology.

What are the main stages of fracture healing?

The fracture healing process can be divided into four main stages:

  1. Inflammation
  2. Soft callus formation
  3. Hard callus formation
  4. Bone remodeling

During the inflammatory stage, a hematoma forms at the fracture site, providing a scaffold for cellular infiltration. This is followed by the formation of a soft callus, composed primarily of cartilage and fibrous tissue. The soft callus is gradually replaced by a hard callus of woven bone, which is eventually remodeled into lamellar bone, restoring the bone’s original structure and function.

The Crucial Role of Blood Supply in Fracture Healing

Adequate blood supply is essential for successful fracture healing. How does vascularization impact the healing process?

Vascularization plays a critical role in fracture healing by:

  • Delivering oxygen and nutrients to the healing tissues
  • Facilitating the removal of metabolic waste products
  • Providing a conduit for inflammatory cells and growth factors
  • Supporting the migration and differentiation of osteoprogenitor cells

The periosteum, a highly vascularized membrane covering the bone surface, is a primary source of blood supply during fracture healing. Additionally, the intraosseous blood supply and surrounding soft tissues contribute to the vascularization of the fracture site.

Angiogenesis in Fracture Repair

Angiogenesis, the formation of new blood vessels, is a crucial component of fracture healing. Vascular endothelial growth factor (VEGF) is a key mediator of this process, promoting the proliferation and migration of endothelial cells. The hypoxia-inducible factor (HIF) pathway also plays a significant role in regulating angiogenesis during fracture repair.

Pericytes: The Unsung Heroes of Bone Regeneration

Pericytes are perivascular cells that have gained increasing attention in the field of bone regeneration. What role do pericytes play in fracture healing?

Pericytes contribute to fracture healing in several ways:

  • Serving as a potential source of osteoblast progenitor cells
  • Supporting angiogenesis and vascular stability
  • Secreting growth factors and cytokines that promote bone formation
  • Participating in the inflammatory response and tissue remodeling

Recent studies have suggested that pericytes may be a more significant source of osteoblasts than previously thought, highlighting their importance in the bone regeneration process.

The Impact of Muscle Tissue on Fracture Healing

The relationship between muscle tissue and bone healing has been a subject of increasing interest in recent years. How do muscles influence fracture repair?

Muscles contribute to fracture healing through various mechanisms:

  • Providing a rich source of blood supply to the fracture site
  • Secreting growth factors and cytokines that promote bone formation
  • Offering mechanical stimulation that enhances bone regeneration
  • Serving as a potential source of osteoprogenitor cells

Studies have shown that muscle flap coverage can significantly improve bone blood flow and enhance the strength of union at fracture sites, particularly in cases of devascularized bone segments.

Muscle Flaps in Clinical Practice

The use of muscle flaps in the treatment of complex fractures and non-unions has gained popularity in recent years. Clinical studies have demonstrated improved outcomes in cases where muscle flap coverage was employed, particularly in the management of open fractures and infected non-unions.

Factors Contributing to Delayed Union and Non-Union

Despite the remarkable capacity for bone regeneration, some fractures may experience delayed healing or fail to heal altogether. What factors can lead to delayed union or non-union of fractures?

Several factors can impair fracture healing, including:

  • Inadequate blood supply to the fracture site
  • Excessive motion at the fracture site
  • Infection
  • Systemic diseases (e.g., diabetes, osteoporosis)
  • Smoking and alcohol consumption
  • Nutritional deficiencies
  • Certain medications (e.g., non-steroidal anti-inflammatory drugs, corticosteroids)
  • Radiation exposure

Understanding these risk factors is crucial for preventing and managing delayed unions and non-unions in clinical practice.

Innovative Approaches to Enhancing Fracture Healing

As our understanding of the fracture healing process continues to evolve, new therapeutic approaches are being developed to enhance bone regeneration. What are some innovative strategies for promoting fracture healing?

Several promising approaches are currently being investigated:

  • Cell-based therapies using mesenchymal stem cells or induced pluripotent stem cells
  • Growth factor delivery systems (e.g., BMP-2, PDGF, VEGF)
  • Gene therapy targeting key molecular pathways involved in bone formation
  • Biomaterial scaffolds that mimic the natural extracellular matrix
  • Low-intensity pulsed ultrasound (LIPUS) and other biophysical stimulation techniques
  • 3D-printed custom implants and scaffolds

These innovative approaches hold the potential to revolutionize the treatment of complex fractures and improve outcomes for patients with impaired healing capacity.

The Role of Inflammation in Fracture Repair

Inflammation is a critical component of the early stages of fracture healing, but excessive or prolonged inflammation can impair the repair process. How does inflammation impact fracture healing?

The inflammatory response in fracture healing serves several important functions:

  • Initiating the healing cascade through the release of pro-inflammatory cytokines
  • Recruiting inflammatory cells and progenitor cells to the fracture site
  • Stimulating angiogenesis and the formation of granulation tissue
  • Promoting the differentiation of mesenchymal stem cells into osteoblasts and chondrocytes

However, chronic inflammation can lead to excessive bone resorption and impaired bone formation, potentially resulting in delayed union or non-union. Balancing the inflammatory response is crucial for optimal fracture healing.

Modulating Inflammation for Improved Healing

Recent research has focused on developing strategies to modulate the inflammatory response to promote optimal fracture healing. These approaches include:

  • Targeted anti-inflammatory therapies
  • Controlled release of pro-resolution mediators
  • Immunomodulatory biomaterials
  • Dietary interventions to support a balanced inflammatory response

By fine-tuning the inflammatory process, these strategies aim to create an optimal environment for bone regeneration while minimizing the potential negative effects of excessive inflammation.

The Impact of Mechanical Forces on Fracture Healing

Mechanical forces play a crucial role in regulating fracture healing and bone remodeling. How do mechanical stimuli influence the repair process?

Mechanical forces impact fracture healing through various mechanisms:

  • Stimulating cellular mechanotransduction pathways
  • Promoting angiogenesis and vascularization
  • Influencing the differentiation of mesenchymal stem cells
  • Regulating the synthesis and organization of extracellular matrix components
  • Enhancing the alignment and strength of newly formed bone tissue

The concept of mechanobiology has led to the development of various therapeutic approaches that harness mechanical stimuli to enhance fracture healing, such as controlled micromotion devices and external fixation techniques.

Optimizing Mechanical Environment for Fracture Repair

Creating an optimal mechanical environment is essential for successful fracture healing. This involves:

  • Achieving appropriate fracture reduction and stabilization
  • Allowing for controlled micromotion at the fracture site
  • Gradually increasing weight-bearing and functional loading as healing progresses
  • Utilizing rehabilitation protocols that promote bone formation and prevent muscle atrophy

By carefully managing the mechanical environment throughout the healing process, clinicians can significantly improve outcomes and reduce the risk of complications.

The Genetics of Fracture Healing

Genetic factors play a significant role in determining an individual’s capacity for fracture healing. How do genetic variations impact the repair process?

Genetic factors influence fracture healing through various mechanisms:

  • Regulating the expression of key growth factors and signaling molecules
  • Influencing the differentiation and function of bone-forming cells
  • Modulating the inflammatory response and immune system function
  • Affecting bone metabolism and mineral homeostasis
  • Determining the individual’s response to mechanical stimuli

Understanding the genetic basis of fracture healing can help identify patients at risk for impaired healing and guide the development of personalized treatment strategies.

Genetic Biomarkers for Fracture Healing

Recent advances in genomics and molecular biology have led to the identification of potential genetic biomarkers for fracture healing. These biomarkers may help:

  • Predict an individual’s healing potential
  • Guide treatment decisions and surgical planning
  • Monitor the progression of fracture repair
  • Identify targets for therapeutic interventions

As our understanding of the genetic factors influencing fracture healing continues to grow, the potential for personalized medicine approaches in orthopedics becomes increasingly promising.

The Role of Nutrition in Fracture Healing

Proper nutrition is essential for optimal fracture healing. How does diet impact the repair process?

Nutrition plays a crucial role in fracture healing by:

  • Providing the necessary building blocks for new tissue formation
  • Supporting the energy requirements of cellular processes involved in healing
  • Modulating the inflammatory response
  • Influencing bone metabolism and mineral homeostasis
  • Supporting the function of the immune system

Key nutrients that are particularly important for fracture healing include protein, calcium, vitamin D, vitamin C, and various trace minerals such as zinc and copper.

Nutritional Interventions to Enhance Fracture Healing

Several nutritional strategies have been proposed to support and enhance fracture healing:

  • Increased protein intake to support collagen synthesis and tissue repair
  • Calcium and vitamin D supplementation to optimize bone mineralization
  • Antioxidant-rich diets to modulate inflammation and oxidative stress
  • Omega-3 fatty acid supplementation to support a balanced inflammatory response
  • Adequate hydration to support cellular function and nutrient transport

While nutritional interventions alone are unlikely to dramatically accelerate fracture healing in well-nourished individuals, addressing nutritional deficiencies and optimizing dietary intake can significantly improve outcomes, particularly in at-risk populations.

Future Directions in Fracture Healing Research

As our understanding of the complex biology of fracture healing continues to evolve, new avenues for research and therapeutic interventions are emerging. What are some promising areas of investigation in fracture healing research?

Several exciting areas of research are currently being explored:

  • Nanotechnology-based approaches for targeted drug delivery and tissue engineering
  • Advanced imaging techniques for real-time monitoring of fracture healing
  • Artificial intelligence and machine learning applications in fracture management
  • Exosome-based therapies for enhancing bone regeneration
  • Microbiome modulation to optimize the healing environment
  • CRISPR-Cas9 gene editing for correcting genetic defects affecting bone healing
  • Bioprinting of custom bone grafts and tissue-engineered constructs

These innovative approaches hold the potential to revolutionize fracture management and improve outcomes for patients with complex or challenging fractures.

Translating Research into Clinical Practice

While many promising therapies are currently in development, translating these research findings into clinical practice remains a significant challenge. Future efforts should focus on:

  • Conducting large-scale, multicenter clinical trials to validate new therapeutic approaches
  • Developing standardized protocols for the application of novel treatments
  • Addressing regulatory and safety concerns associated with advanced therapies
  • Improving the cost-effectiveness and accessibility of innovative treatments
  • Enhancing collaboration between researchers, clinicians, and industry partners

By addressing these challenges, the field of fracture healing research can continue to advance, ultimately leading to improved patient outcomes and reduced healthcare costs associated with fracture management.

Muscle-bone interactions during fracture healing

1. Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III (severe) open fractures: a new classification of type III open fractures. J Trauma. 1984;24:742–6. [PubMed] [Google Scholar]

2. Marsell R, Einhorn TA. The biology of fracture healing. Injury. 2011;42:551–5. [PMC free article] [PubMed] [Google Scholar]

3. Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA. Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem. 2003;88:873–84. [PubMed] [Google Scholar]

4. Gerstenfeld LC, Alkhiary YM, Krall EA, et al. Three-dimensional reconstruction of fracture callus morphogenesis. J Histochem Cytochem. 2006;54:1215–28. [PubMed] [Google Scholar]

5. Claes L, Recknagel S, Ignatius A. Fracture healing under healthy and inflammatory conditions. Nat Rev Rheumatol. 2012;8:133–43. [PubMed] [Google Scholar]

6. Schipani E, Maes C, Carmeliet G, Semenza GL. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J Bone Miner Res. 2009;24:1347–53. [PMC free article] [PubMed] [Google Scholar]

7. Glowacki J. Angiogenesis in fracture repair. Clin Orthop Relat Res. 1998:S82–9. [PubMed] [Google Scholar]

8. Zelzer E, Olsen BR. Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair. Curr Top Dev Biol. 2005;65:169–87. [PubMed] [Google Scholar]

9. Kristensen HB, Andersen TL, Marcussen N, Rolighed L, Delaisse JM. Increased presence of capillaries next to remodeling sites in adult human cancellous bone. J Bone Miner Res. 2013;28:574–85. [PubMed] [Google Scholar]

10. Colnot C, Zhang X, Knothe Tate ML. Current insights on the regenerative potential of the periosteum: molecular, cellular, and endogenous engineering approaches. J Orthop Res. 2012;30:1869–78. [PMC free article] [PubMed] [Google Scholar]

11. Zuscik MJ, Hilton MJ, Zhang X, Chen D, O’Keefe RJ. Regulation of chondrogenesis and chondrocyte differentiation by stress. J Clin Invest. 2008;118:429–38. [PMC free article] [PubMed] [Google Scholar]

12. Rhinelander FW. Tibial blood supply in relation to fracture healing. Clin Orthop Relat Res. 1974:34–81. [PubMed] [Google Scholar]

13. Laroche M. Intraosseous circulation from physiology to disease. Joint Bone Spine. 2002;69:262–9. [PubMed] [Google Scholar]

14. Brighton CT, Lorich DG, Kupcha R, Reilly TM, Jones AR, Woodbury RA., 2nd The pericyte as a possible osteoblast progenitor cell. Clin Orthop Relat Res. 1992:287–99. [PubMed] [Google Scholar]

15. Diaz-Flores L, Gutierrez R, Lopez-Alonso A, Gonzalez R, Varela H. Pericytes as a supplementary source of osteoblasts in periosteal osteogenesis. Clin Orthop Relat Res. 1992;275:280–6. [PubMed] [Google Scholar]

16. Mills SJ, Cowin AJ, Kaur P. Pericytes, mesenchymal stem cells and the wound healing process. Cells. 2013;2:621–34. [PMC free article] [PubMed] [Google Scholar]

17. Kumar A, Salimath BP, Stark GB, Finkenzeller G. Platelet-derived growth factor receptor signaling is not involved in osteogenic differentiation of human mesenchymal stem cells. Tissue Eng Part A. 2010;16:983–93. [PubMed] [Google Scholar]

18. Lu C, Miclau T, Hu D, Marcucio RS. Ischemia leads to delayed union during fracture healing: a mouse model. J Orthop Res. 2007;25:51–61. [PMC free article] [PubMed] [Google Scholar]

19. Green N, French S, Rodriquez G, Hays M, Fingerhut A. Radiation-induced delayed union of fractures. Radiology. 1969;93:635–41. [PubMed] [Google Scholar]

20. Liu R, Schindeler A, Little DG. The potential role of muscle in bone repair. J Musculoskelet Neuronal Interact. 2010;10:71–6. [PubMed] [Google Scholar]

21. Richards RR, Schemitsch EH. Effect of muscle flap coverage on bone blood flow following devascularization of a segment of tibia: an experimental investigation in the dog. J Orthop Res. 1989;7:550–8. [PubMed] [Google Scholar]

22. Richards RR, McKee MD, Paitich CB, Anderson GI, Bertoia JT. A comparison of the effects of skin coverage and muscle flap coverage on the early strength of union at the site of osteotomy after devascularization of a segment of canine tibia. J Bone Joint Surg Am. 1991;73:1323–30. [PubMed] [Google Scholar]

23. Richards RR, Orsini EC, Mahoney JL, Verschuren R. The influence of muscle flap coverage on the repair of devascularized tibial cortex: an experimental investigation in the dog. Plast Reconstr Surg. 1987;79:946–58. [PubMed] [Google Scholar]

24. Choi P, Ogilvie C, Thompson Z, Miclau T, Helms JA. Cellular and molecular characterization of a murine non-union model. J Orthop Res. 2004;22:1100–7. [PubMed] [Google Scholar]

25. Brownlow HC, Reed A, Simpson AH. The vascularity of atrophic non-unions. Injury. 2002;33:145–50. [PubMed] [Google Scholar]

26. Reed AA, Joyner CJ, Brownlow HC, Simpson AH. Human atrophic fracture non-unions are not avascular. J Orthop Res. 2002;20:593–9. [PubMed] [Google Scholar]

27. Harry LE, Sandison A, Paleolog EM, Hansen U, Pearse MF, Nanchahal J. Comparison of the healing of open tibial fractures covered with either muscle or fasciocutaneous tissue in a murine model. J Orthop Res. 2008;26:1238–44. [PubMed] [Google Scholar]

28. Urist MR. Bone: formation by autoinduction. Science. 1965;150:893–9. [PubMed] [Google Scholar]

29. Chan JK, Harry L, Williams G, Nanchahal J. Soft-tissue reconstruction of open fractures of the lower limb: muscle versus fasciocutaneous flaps. Plast Reconstr Surg. 2012;130:284e–95e. [PMC free article] [PubMed] [Google Scholar]

30. Stein H, Perren SM, Cordey J, Kenwright J, Mosheiff R, Francis MJ. The muscle bed–a crucial factor for fracture healing: a physiological concept. Orthopedics. 2002;25:1379–83. [PubMed] [Google Scholar]

31. Davis TA, Lazdun Y, Potter BK, Forsberg JA. Ectopic bone formation in severely combat-injured orthopedic patients – a hematopoietic niche. Bone. 2013;56:119–26. [PubMed] [Google Scholar]

32. DeLee J, Ferrari A, Charnley J. Ectopic bone formation following low friction arthroplasty of the hip. Clin Orthop Relat Res. 1976;121:53–9. [PubMed] [Google Scholar]

33. Kaplan FS, Lounev VY, Wang H, Pignolo RJ, Shore EM. Fibrodysplasia ossificans progressiva: a blueprint for metamorphosis. Ann N Y Acad Sci. 2011;1237:5–10. [PMC free article] [PubMed] [Google Scholar]

34. Kato S, Sangadala S, Tomita K, Titus L, Boden SD. A synthetic compound that potentiates bone morphogenetic protein-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype. Mol Cell Biochem. 2011;349:97–106. [PMC free article] [PubMed] [Google Scholar]

35. Wong E, Sangadala S, Boden SD, et al. A novel low-molecular-weight compound enhances ectopic bone formation and fracture repair. J Bone Joint Surg Am. 2013;95:454–61. [PMC free article] [PubMed] [Google Scholar]

36. Cairns DM, Liu R, Sen M, et al. Interplay of Nkx3.2, Sox9 and Pax3 regulates chondrogenic differentiation of muscle progenitor cells. PLoS One. 2012;7:e39642. [PMC free article] [PubMed] [Google Scholar]

37. Lee JY, Qu-Petersen Z, Cao B, et al. Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing. J Cell Biol. 2000;150:1085–100. [PMC free article] [PubMed] [Google Scholar]

38. Evans CH, Liu FJ, Glatt V, et al. Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage. Eur Cell Mater. 2009;18:96–111. [PMC free article] [PubMed] [Google Scholar]

39. Gao X, Usas A, Tang Y, et al. A comparison of bone regeneration with human mesenchymal stem cells and muscle-derived stem cells and the critical role of BMP. Biomaterials. 2014;35:6859–70. [PMC free article] [PubMed] [Google Scholar]

40. Sondag GR, Salihoglu S, Lababidi SL, et al. Osteoactivin induces transdifferentiation of C2C12 myoblasts into osteoblasts. J Cell Physiol. 2014;229:955–66. [PubMed] [Google Scholar]

41. Glass GE, Chan JK, Freidin A, Feldmann M, Horwood NJ, Nanchahal J. TNF-alpha promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells. Proc Natl Acad Sci U S A. 2011;108:1585–90. [PMC free article] [PubMed] [Google Scholar]

42. Jankowski RJ, Deasy BM, Huard J. Muscle-derived stem cells. Gene Ther. 2002;9:642–7. [PubMed] [Google Scholar]

43. Asakura A, Komaki M, Rudnicki M. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation. 2001;68:245–53. [PubMed] [Google Scholar]

44. Huang S, Jia S, Liu G, Fang D, Zhang D. Osteogenic differentiation of muscle satellite cells induced by platelet-rich plasma encapsulated in three-dimensional alginate scaffold. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114:S32–40. [PubMed] [Google Scholar]

45. Wu X, Rathbone CR. Satellite cell functional alterations following cutaneous burn in rats include an increase in their osteogenic potential. J Surg Res. 2013;184:e9–16. [PubMed] [Google Scholar]

46. Hashimoto N, Kiyono T, Wada MR, et al. Osteogenic properties of human myogenic progenitor cells. Mech Dev. 2008;125:257–69. [PubMed] [Google Scholar]

47. Malizos KN, Papatheodorou LK. The healing potential of the periosteum molecular aspects. Injury. 2005;36(Suppl 3):S13–9. [PubMed] [Google Scholar]

48. Dwek JR. The periosteum: what is it, where is it, and what mimics it in its absence? Skeletal Radiol. 2010;39:319–23. [PMC free article] [PubMed] [Google Scholar]

49. Zhang X, Xie C, Lin AS, et al. Periosteal progenitor cell fate in segmental cortical bone graft transplantations: implications for functional tissue engineering. J Bone Miner Res. 2005;20:2124–37. [PMC free article] [PubMed] [Google Scholar]

50. Hutmacher DW, Sittinger M. Periosteal cells in bone tissue engineering. Tissue Eng. 2003;9(Suppl 1):S45–64. [PubMed] [Google Scholar]

51. Liu R, Birke O, Morse A, et al. Myogenic progenitors contribute to open but not closed fracture repair. BMC Musculoskelet Disord. 2011;12:288. [PMC free article] [PubMed] [Google Scholar]

52. Kaufman H, Reznick A, Stein H, Barak M, Maor G. The biological basis of the bone-muscle inter-relationship in the algorithm of fracture healing. Orthopedics. 2008;31:751. [PubMed] [Google Scholar]

53. Utvag SE, Grundnes O, Reikeras O. Early muscle-periosteal lesion inhibits fracture healing in rats. Acta Orthop Scand. 1999;70:62–6. [PubMed] [Google Scholar]

54. Bortoluzzi S, Scannapieco P, Cestaro A, Danieli GA, Schiaffino S. Computational reconstruction of the human skeletal muscle secretome. Proteins. 2006;62:776–92. [PubMed] [Google Scholar]

55. Norheim F, Raastad T, Thiede B, Rustan AC, Drevon CA, Haugen F. Proteomic identification of secreted proteins from human skeletal muscle cells and expression in response to strength training. Am J Physiol Endocrinol Metab. 2011;301:E1013–21. [PubMed] [Google Scholar]

56. Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454:961–7. [PMC free article] [PubMed] [Google Scholar]

57. Kon T, Cho TJ, Aizawa T, et al. Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. J Bone Miner Res. 2001;16:1004–14. [PubMed] [Google Scholar]

58. Ai-Aql ZS, Alagl AS, Graves DT, Gerstenfeld LC, Einhorn TA. Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis. J Dent Res. 2008;87:107–18. [PMC free article] [PubMed] [Google Scholar]

59. Mountziaris PM, Mikos AG. Modulation of the inflammatory response for enhanced bone tissue regeneration. Tissue Eng Part B Rev. 2008;14:179–86. [PMC free article] [PubMed] [Google Scholar]

60. Park S, Silva M, Bahk W, McKellop H, Lieberman J. Effect of repeated irrigation and debridement on fracture healing in an animal model. J Orthop Res. 2002;20:1197–204. [PubMed] [Google Scholar]

61. Grundnes O, Reikeras O. The importance of the hematoma for fracture healing in rats. Acta Orthop Scand. 1993;64:340–2. [PubMed] [Google Scholar]

62. Glass GE, Chan JK, Freidin A, Feldmann M, Horwood NJ, Nanchahal J. TNF-ápromotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells. Proceedings of the National Academy of Sciences. 2011;108:1585–90. [PMC free article] [PubMed] [Google Scholar]

63. Hamrick MW. A role for myokines in muscle-bone interactions. Exerc Sport Sci Rev. 2011;39:43–7. [PMC free article] [PubMed] [Google Scholar]

64. Kalajzic I, Staal A, Yang WP, et al. Expression profile of osteoblast lineage at defined stages of differentiation. J Biol Chem. 2005;280:24618–26. [PubMed] [Google Scholar]

65. Andrew JG, Hoyland J, Freemont AJ, Marsh D. Insulinlike growth factor gene expression in human fracture callus. Calcif Tissue Int. 1993;53:97–102. [PubMed] [Google Scholar]

66. Luginbuehl V, Zoidis E, Meinel L, von Rechenberg B, Gander B, Merkle HP. Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep. Eur J Pharm Biopharm. 2013;85:99–106. [PubMed] [Google Scholar]

67. Meinel L, Zoidis E, Zapf J, et al. Localized insulin-like growth factor I delivery to enhance new bone formation. Bone. 2003;33:660–72. [PubMed] [Google Scholar]

68. Ljunghall S, Johansson AG, Burman P, Kampe O, Lindh E, Karlsson FA. Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis. J Intern Med. 1992;232:59–64. [PubMed] [Google Scholar]

69. Liu JM, Zhao HY, Ning G, et al. IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab. 2008;26:159–64. [PubMed] [Google Scholar]

70. Hill M, Goldspink G. Expression and splicing of the insulin- like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage. J Physiol. 2003;549:409–18. [PMC free article] [PubMed] [Google Scholar]

71. Marsh DR, Criswell DS, Hamilton MT, Booth FW. Association of insulin-like growth factor mRNA expressions with muscle regeneration in young, adult, and old rats. Am J Physiol. 1997;273:R353–8. [PubMed] [Google Scholar]

72. Hammers DW, Merritt EK, Matheny RW. , Jr et al. Functional deficits and insulin-like growth factor-I gene expression following tourniquet-induced injury of skeletal muscle in young and old rats. J Appl Physiol 1985. 2008;105:1274–81. [PMC free article] [PubMed] [Google Scholar]

73. Shavlakadze T, Winn N, Rosenthal N, Grounds MD. Reconciling data from transgenic mice that overexpress IGFI specifically in skeletal muscle. Growth Horm IGF Res. 2005;15:4–18. [PubMed] [Google Scholar]

74. Machida S, Booth FW. Insulin-like growth factor 1 and muscle growth: implication for satellite cell proliferation. Proc Nutr Soc. 2004;63:337–40. [PubMed] [Google Scholar]

75. Han B, Tong J, Zhu MJ, Ma C, Du M. Insulin-like growth factor-1 (IGF-1) and leucine activate pig myogenic satellite cells through mammalian target of rapamycin (mTOR) pathway. Mol Reprod Dev. 2008;75:810–7. [PubMed] [Google Scholar]

76. Mourkioti F, Rosenthal N. IGF-1, inflammation and stem cells: interactions during muscle regeneration. Trends Immunol. 2005;26:535–42. [PubMed] [Google Scholar]

77. Lee WJ. IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down-regulation of TLR4 Signaling. Immune Netw. 2011;11:223–6. [PMC free article] [PubMed] [Google Scholar]

78. Elkasrawy M, Fulzele S, Bowser M, Wenger K, Hamrick M. Myostatin (GDF-8) inhibits chondrogenesis and chondrocyte proliferation in vitro by suppressing Sox-9 expression. Growth Factors. 2011;29:253–62. [PMC free article] [PubMed] [Google Scholar]

79. Hamrick MW, Arounleut P, Kellum E, Cain M, Immel D, Liang LF. Recombinant myostatin (GDF-8) propeptide enhances the repair and regeneration of both muscle and bone in a model of deep penetrant musculoskeletal injury. J Trauma. 2010;69:579–83. [PMC free article] [PubMed] [Google Scholar]

80. Hamrick MW, McPherron AC, Lovejoy CO, Hudson J. Femoral morphology and cross-sectional geometry of adult myostatin-deficient mice. Bone. 2000;27:343–9. [PubMed] [Google Scholar]

81. Hamrick MW, McPherron AC, Lovejoy CO. Bone mineral content and density in the humerus of adult myostatin- deficient mice. Calcif Tissue Int. 2002;71:63–8. [PubMed] [Google Scholar]

82. Hamrick MW. Increased bone mineral density in the femora of GDF8 knockout mice. Anat Rec A Discov Mol Cell Evol Biol. 2003;272:388–91. [PubMed] [Google Scholar]

83. Bialek P, Parkington J, Li X, et al. A myostatin and activin decoy receptor enhances bone formation in mice. Bone. 2014;60:162–71. [PubMed] [Google Scholar]

84. Elkasrawy M, Immel D, Wen X, Liu X, Liang LF, Hamrick MW. Immunolocalization of myostatin (GDF-8) following musculoskeletal injury and the effects of exogenous myostatin on muscle and bone healing. J Histochem Cytochem. 2012;60:22–30. [PMC free article] [PubMed] [Google Scholar]

85. Elkasrawy MN, Hamrick MW. Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact. 2010;10:56–63. [PMC free article] [PubMed] [Google Scholar]

86. Kellum E, Starr H, Arounleut P, et al. Myostatin (GDF- 8) deficiency increases fracture callus size, Sox-5 expression, and callus bone volume. Bone. 2009;44:17–23. [PMC free article] [PubMed] [Google Scholar]

87. Gazzerro E, Canalis E. Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord. 2006;7:51–65. [PubMed] [Google Scholar]

88. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors. 2004;22:233–41. [PubMed] [Google Scholar]

89. Wozney JM. Bone Morphogenetic Proteins. Progress in Growth Factor Research. 1989;1:267–80. [PubMed] [Google Scholar]

90. Yamaguchi A, Ishizuya T, Kintou N, et al. Effects of BMP-2, BMP-4, and BMP-6 on osteoblastic differentiation of bone marrow-derived stromal cell lines, ST2 and MC3T3-G2/PA6. Biochem Biophys Res Commun. 1996;220:366–71. [PubMed] [Google Scholar]

91. Lavery K, Swain P, Falb D, Alaoui-Ismaili MH. BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow- derived mesenchymal stem cells. J Biol Chem. 2008;283:20948–58. [PMC free article] [PubMed] [Google Scholar]

92. Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J. 2011;11:471–91. [PubMed] [Google Scholar]

93. Carragee EJ, Chu G, Rohatgi R, et al. Cancer Risk After Use of Recombinant Bone Morphogenetic Protein-2 for Spinal Arthrodesis. J Bone Joint Surg Am. 2013;95:1537–45. [PubMed] [Google Scholar]

94. Kessler E, Takahara K, Biniaminov L, Brusel M, Greenspan DS. Bone morphogenetic protein-1: the type I procollagen C-proteinase. Science. 1996;271:360–2. [PubMed] [Google Scholar]

95. Jackson WM, Aragon AB, Onodera J, et al. Cytokine expression in muscle following traumatic injury. J Orthop Res. 2011;29:1613–20. [PMC free article] [PubMed] [Google Scholar]

96. Villarreal XC, Mann KG, Long GL. Structure of human osteonectin based upon analysis of cDNA and genomic sequences. Biochemistry. 1989;28:6483–91. [PubMed] [Google Scholar]

97. Brekken RA, Sage EH. SPARC, a matricellular protein: at the crossroads of cell-matrix communication. Matrix Biol. 2001;19:816–27. [PubMed] [Google Scholar]

98. Delany AM, Amling M, Priemel M, Howe C, Baron R, Canalis E. Osteopenia and decreased bone formation in osteonectin-deficient mice. J Clin Invest. 2000;105:1325. [PMC free article] [PubMed] [Google Scholar]

99. Jorgensen LH, Petersson SJ, Sellathurai J, et al. Secreted protein acidic and rich in cysteine (SPARC) in human skeletal muscle. J Histochem Cytochem. 2009;57:29–39. [PMC free article] [PubMed] [Google Scholar]

100. Yamazaki M, Majeska R, Moriya J. Role of osteonectin during fracture healing. Trans Orthop Res Soc. 1997;22:254. [Google Scholar]

101. Hiltunen A, Metsaranta M, Virolainen P, Aro HT, Vuorio E. Retarded chondrogenesis in transgenic mice with a type II collagen defect results in fracture healing abnormalities. Dev Dyn. 1994;200:340–9. [PubMed] [Google Scholar]

102. Jingushi S, Joyce ME, Bolander ME. Genetic expression of extracellular matrix proteins correlates with histologic changes during fracture repair. J Bone Miner Res. 1992;7:1045–55. [PubMed] [Google Scholar]

103. Grimston SK, Goldberg DB, Watkins M, Brodt MD, Silva MJ, Civitelli R. Connexin43 deficiency reduces the sensitivity of cortical bone to the effects of muscle paralysis. J Bone Miner Res. 2011;26:2151–60. [PMC free article] [PubMed] [Google Scholar]

104. Grimston SK, Brodt MD, Silva MJ, Civitelli R. Attenuated response to in vivo mechanical loading in mice with conditional osteoblast ablation of the connexin43 gene (Gja1) J Bone Miner Res. 2008;23:879–86. [PMC free article] [PubMed] [Google Scholar]

105. Gross TS, Poliachik SL, Prasad J, Bain SD. The effect of muscle dysfunction on bone mass and morphology. J Musculoskelet Neuronal Interact. 2010;10:25–34. [PubMed] [Google Scholar]

106. Ijiri K, Ma YF, Jee WS, Akamine T, Liang X. Adaptation of non-growing former epiphysis and metaphyseal trabecular bones to aging and immobilization in rat. Bone. 1995;17:207S–12S. [PubMed] [Google Scholar]

107. Tuukkanen J, Wallmark B, Jalovaara P, Takala T, Sjogren S, Vaananen K. Changes induced in growing rat bone by immobilization and remobilization. Bone. 1991;12:113–8. [PubMed] [Google Scholar]

108. Liu D, Zhao CQ, Li H, Jiang SD, Jiang LS, Dai LY. Effects of spinal cord injury and hindlimb immobilization on sublesional and supralesional bones in young growing rats. Bone. 2008;43:119–25. [PubMed] [Google Scholar]

109. Hao Y, Ma Y, Wang X, Jin F, Ge S. Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur. J Orthop Res. 2012;30:574–80. [PubMed] [Google Scholar]

110. Poliachik SL, Bain SD, Threet D, Huber P, Gross TS. Transient muscle paralysis disrupts bone homeostasis by rapid degradation of bone morphology. Bone. 2010;46:18–23. [PMC free article] [PubMed] [Google Scholar]

111. Thomsen JS, Christensen LL, Vegger JB, Nyengaard JR, Bruel A. Loss of bone strength is dependent on skeletal site in disuse osteoporosis in rats. Calcif Tissue Int. 2012;90:294–306. [PubMed] [Google Scholar]

112. Ellman R, Grasso DJ, van Vliet M, et al. Combined effects of botulinum toxin injection and hind limb unloading on bone and muscle. Calcif Tissue Int. 2014;94:327–37. [PMC free article] [PubMed] [Google Scholar]

113. Aliprantis AO, Stolina M, Kostenuik PJ, et al. Transient muscle paralysis degrades bone via rapid osteoclastogenesis. FASEB J. 2012;26:1110–8. [PMC free article] [PubMed] [Google Scholar]

114. Zachs SI, Sheff MF. Periosteal and metaplastic bone formation in mouse minced muscle regeneration. Lab Invest. 1982;46:405–12. [PubMed] [Google Scholar]

115. Utvag SE, Grundnes O, Reikeras O. Effects of lesion between bone, periosteum and muscle on fracture healing in rats. Acta Orthop Scand. 1998;69:177–80. [PubMed] [Google Scholar]

116. Utvag SE, Grundnes O, Rindal DB, Reikeras O. Influence of extensive muscle injury on fracture healing in rat tibia. J Orthop Trauma. 2003;17:430–5. [PubMed] [Google Scholar]

117. Utvag SE, Iversen KB, Grundnes O, Reikeras O. Poor muscle coverage delays fracture healing in rats. Acta Orthop Scand. 2002;73:471–4. [PubMed] [Google Scholar]

118. Willett NJ, Mon-Tzu LA, Uhrig BA, et al. Attenuated human bone morphogenetic protein-2-mediated bone regeneration in a rat model of composite bone and muscle injury. Tissue Eng Pt C-Meth. 2013;19:316–25. [PMC free article] [PubMed] [Google Scholar]

119. Gustilo R, Anderson J. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses. J Bone Joint Surg Am. 1976;58:453–8. [PubMed] [Google Scholar]

120. Papakostidis C, Kanakaris NK, Pretel J, Faour O, Morell DJ, Giannoudis PV. Prevalence of complications of open tibial shaft fractures stratified as per the Gustilo–Anderson classification. Injury. 2011;42:1408–15. [PubMed] [Google Scholar]

121. Giannoudis PV, Harwood PJ, Kontakis G, et al. Longterm quality of life in trauma patients following the full spectrum of tibial injury (fasciotomy, closed fracture, grade IIIB/IIIC open fracture and amputation) Injury. 2009;40:213–9. [PubMed] [Google Scholar]

122. Landry PS, Marino AA, Sadasivan KK, Albright JA. Effect of soft-tissue trauma on the early periosteal response of bone to injury. J Trauma. 2000;48:479–83. [PubMed] [Google Scholar]

123. Duda GN, Taylor WR, Winkler T, et al. Biomechanical, microvascular, and cellular factors promote muscle and bone regeneration. Exerc Sport Sci Rev. 2008;36:64–70. [PubMed] [Google Scholar]

124. Gopal S, Majumder S, Batchelor AG, Knight SL, De Boer P, Smith RM. Fix and flap: the radical orthopaedic and plastic treatment of severe open fractures of the tibia. J Bone Joint Surg Br. 2000;82:959–66. [PubMed] [Google Scholar]

125. Reverte MM, Dimitriou R, Kanakaris NK, Giannoudis PV. What is the effect of compartment syndrome and fasciotomies on fracture healing in tibial fractures?Injury. 2011;42:1402–7. [PubMed] [Google Scholar]

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Fractures | Radiography | Health-improving center Sharitel in Kyiv

A bone fracture is a violation of the integrity of the bone (complete or partial). Most fractures occur as a result of trauma, although fractures of the vertebrae and other skeletal bones in osteoporosis can occur spontaneously without significant trauma.

Fracture risk factors:

• Old age

• Extreme sports

• Hormonal factors (ovarian dysfunction, menopause, thyroid and parathyroid diseases, diabetes mellitus, etc.)

• Medications (glucocorticoids, chemotherapy, etc.)

• Frequent pregnancies or infertility

• Malnutrition

• Smoking

• Alcohol abuse

Post-traumatic fracture
Symptoms of a post-traumatic fracture vary significantly depending on the location, severity, damage to the bone (with or without fragments) and surrounding tissues.
Distinguish:

• simple fracture – without damage or with minor damage to surrounding tissues;

• open fracture – the bone, having broken through the skin, came out;

• compound or comminuted fracture – the bone is broken in several places;

• fracture in the bone.

If you suddenly (especially after an injury) develop the following symptoms, you need to see a doctor as soon as possible, as a fracture is likely.

• Pain

• Loss of ability to control the limb

• Unnatural position of the broken part

• Swelling at the fracture site

• Sound of friction of bone fragments

• Muscle spasm at the fracture site

Diagnosis of a fracture

At Health Center “Sharitel” , radiography is used for diagnosis, and if necessary, a referral for CT or MRI is possible.

Fracture treatment

After establishing the localization of the fracture, the bone fragments are repositioned and a splint is applied. With closed fractures, in some cases, skin necrosis develops as a result of direct trauma or pressure from bone fragments from the inside. Thus, a closed fracture may turn into an open fracture in a few days .

Fracture complications:

• wound suppuration

• osteomyelitis

• anaerobe acute infection

• shock

• fat embolism

• with combined damage to the great vessels – anemia

• Incorrect fusion of bone fragments

• Ununited fracture and false joint

Sequelae of fractures

Quite often, after the fusion of bone fragments, patients continue to experience pain in the bones and joints, swelling of the damaged area, impaired movement, flexion contractures, atrophy ia nearby muscles.

Rehabilitation complex helps to restore dysfunction. For this, physiotherapy , water and mud therapy, 9 are used.0003 massage , exercise therapy, reflexology, etc.

10/07/2018

Pain syndrome in vertebral body fractures complicating the course of systemic osteoporosis | Rodionova

Fractures of the vertebral bodies are referred to as “fractures-markers” of osteoporosis, but due to the asymptomatic course [1], three quarters of patients do not seek medical help, and subsequent pain symptoms are explained by the presence of degenerative changes in the spine. At the same time, these pain sensations are primarily due to a fracture, since its presence leads to additional overload of the facet joint and, as a result, overstretching of the capsular-ligamentous apparatus of the joint and the development of degenerative arthritis. Pain in a fracture of the vertebral body, in contrast to osteochondrosis, appears only under static load, which is associated with the reaction of sensitive nerve fibers to microfractures of the trabeculae, the number of which increases against the background of BMD deficiency and a decrease in the strength of the remaining bone structures in the compressed vertebra. While the density of sensory nerve fibers in the tissue does not decrease [2].

In cases where patients associate pain in the spine with a fracture of the vertebral body, it appears suddenly in the midst of full health and patients may indicate the circumstances that preceded the onset of pain. Most often, this is a lifting of gravity, sometimes just a tilt of the body or a sharp turn, often there are no indications of a traumatic moment. Pain in these cases is felt at the level of the damaged vertebra and, if localized in the thoracic region, can be girdle [3], which requires differential diagnosis with myocardial infarction, pleurisy, and acute disease of the abdominal organs. Acute pain in a fracture of the vertebral body is due to periosteal hemorrhage, an excessive number of simultaneously occurring microfractures of the trabeculae, excessive tension of the ligaments due to these changes, and spasm of the paraspinal muscles. The lack of treatment of osteoporosis in such cases not only increases the risk of new fractures of the vertebral bodies, but also contributes to the formation of chronic pain, which is a consequence of mechanical compression of the ligaments and muscles due to kyphosis of the thoracic spine, excessive tension of the ligaments due to a decrease in growth and the development of arthritis of the intervertebral joints , shortening and increasing spasm of the paraspinal muscles due to a decrease in growth [3]. Some patients with multiple fractures of the vertebral bodies indicate pain “in all bones”, which occurs with any concussion [4]. A feature of chronic pain in fractures of the vertebral bodies is its “intermittent” nature: after 3-4 months, its intensity decreases even without treatment, but then the inevitable exacerbation follows, as the spinal deformity progresses: thoracic kyphosis increases, lumbar hyperlordosis is formed or, conversely, straightens. department of the spine; due to kyphosis of the thoracic region, hyperlordosis of the cervical spine develops, with neck muscle tension and occipital pain. Subsequently, due to the shortening of the torso and the pressure of the ribs on the iliac crests (costal arches “sit down” on the wings of the pelvic bones), pronounced skin folds form on the lateral surface of the chest and pain appears in the lateral parts of the body [5]. Due to overstretching of the capsular-ligamentous apparatus of the facet joints, the localization of pain does not always correspond to the level of the fracture [6]. Thoracic kyphosis, as a result of fractures of the vertebral bodies of the thoracic spine, is formed gradually and is accompanied by increasing weakness of the muscles of the interscapular and paravertebral region, which can cause progression of lumbar scoliosis and a decrease in height by 10-15 cm. An indicator of a decrease in growth is the appearance of a difference between the distances of the symphysis foot and head-symphysis (normal distances are equal).

In systemic osteoporosis, palpation of the spinous processes of the vertebrae is often painless, there may also be a negative test with axial load (pressure on the head or shoulder girdle), but compression of the chest may be painful. These tests must be performed carefully to avoid new fractures of the vertebral bodies.

In lumbar vertebral body fractures, limitation of movement in the lumbar spine may appear, and patients try to support the trunk in an upright position with the help of hands or a cane, especially during fresh attacks of pain. It should also be noted that there is a change with age in the perception and response to pain, the cause of which remains unclear. According to some researchers, this may be due to an increase in the pain threshold in the elderly. [7] The lack of treatment of osteoporosis in case of a fracture that has already occurred serves as a factor in the further progression of the disease and the increase in both symptoms and new fractures, therefore, all patients over 50 years of age with an indication of the above complaints or symptoms should perform an x-ray of the thoracic and lumbar regions to clarify the diagnosis of osteoporosis spine (clarification of the degree of compression of the vertebral bodies) and X-ray densitometry to clarify the magnitude of the loss of BMD [8]. After assessing calcium homeostasis and remodeling markers, it is necessary to start treating osteoporosis with drugs to correct bone remodeling disorders (the principles for prescribing these drugs are set out in the clinical guidelines of the Russian Association for Osteoporosis and the Russian Association of Endocrinologists) [9]. However, at the initial stage, pain relief and prevention of repeated fractures of the vertebral bodies require an integrated approach, which reduces the time spent on bed rest, since prolonged unloading can become a factor in the progression of the disease, deterioration of physical condition, causes muscle hypotrophy, leads to the development of bedsores, deep vein thrombosis , respiratory diseases, disorientation and depression [10]. For this purpose, various painkillers are used [11], unloading of the spinal column with the help of orthoses [12], in the absence of contraindications – physiotherapy [13,14]. The duration of bed rest in case of a fracture of the vertebral body due to osteoporosis should be minimal (no more than 2-3 days) and without restrictions, i.e. patients are allowed to get up in a corset for a short time [15,16]. Pain relief during this period is also achieved using a short course of oral or injectable forms of non-steroidal anti-inflammatory drugs (NSAIDs), centrally acting muscle relaxants [17]. The latter reduce muscle spasm and promote sleep, improve blood circulation in spasmodic muscles, break the vicious circle of “spasm-pain-spasm”, have a membrane stabilizing effect and, accordingly, pronounced analgesic and muscle relaxant effects. The use of tolperisone in combination therapy with NSAIDs can reduce the dose of the latter, reducing the risk of side effects [18]. It is possible to use local anesthesia in the form of patches with anesthetics and / or cold compresses (applications with dimexide), paravertebral blockades of the fracture area with local anesthetics [11]. Verticalization of the patient with the help of corsets is recommended from 2-3 days after the injury. The main effect of the corset in fractures of the vertebral bodies due to osteoporosis is an increase in intra-abdominal pressure, which allows you to unload the vertebral bodies and thereby not only reduce pain, but also prevent the risk of new fractures. Corsets reduce pain by limiting the mobility of the affected spine, thereby contributing to the early recovery of physical activity [19]. The main criteria for choosing a corset are the level of vertebral fracture, the degree of compression, the intensity of the pain syndrome, and the patient’s overall activity [20].

In case of fractures in the lumbar spine, a lumbosacral corset of medium rigidity is recommended, in case of fractures of the thoracic spine, in addition, the Spinomed thoracolumbar corset can be recommended, which provides straightening of the spinal column and reduces the severity of kyphosis due to activation of the back extensors, this corset also contributes to stimulation of the work of the paravertebral muscles through the inclusion of biofeedback. (Figure 1). In patients with fractures of the vertebral bodies due to osteoporosis, wearing a corset throughout the day does not lead to muscle atrophy, provided that daily walking is at least 1.5-2 hours a day and daily exercise therapy in the “lying” and “sitting” positions.

It is also possible to use support devices on wheels with a hand brake. In this case, by straightening the back and reducing the load on the spine, it not only reduces pain during movement, but also reduces the risk of new fractures [21]. To reduce pain in the lateral parts of the body, special soft belts can be recommended, which reduce the contact of bone structures [22].

Figure 1. Spinomed IV front and back view.

In patients with fractures of the vertebral bodies, it is necessary from the first day to prescribe exercises for neuromuscular stabilization of the thoracolumbar spine that do not require verticalization (passive and active exercises with mobilization of the upper and lower extremities and the cervical spine). Exercise therapy reduces the severity of pain by increasing the tone of the extensor muscles and improving coordination. Gentle exercises in the supine position with a pillow under the pelvis help prevent the progression of vertebral deformity, restore posture, and reduce painful kyphotic deformity [23].

After verticalization, exercise therapy is prescribed to strengthen the pectoral and intercostal muscles. In patients with fractures of the vertebral bodies due to osteoporosis, it is extremely important to develop a pattern of movements while maintaining a straight posture in order to reduce the load on the spine and reduce the risk of subsequent fractures. Hard work, heavy lifting and tilting forward and to the sides are excluded [24]. The general principles of exercise in osteoporosis [25] are:

  1. exercise selection and intensity should be adapted to the individual patient in order to avoid undue stress on the spine and cause new injury
  2. exercises should be aimed at stretching the muscles and strengthening the muscle group that extends the spine; limitation of exercises with flexion and rotation of the spine;
  3. exercises are performed carefully at a slow pace without sudden movements;
  4. when exercising, patients should try to stick out their chest, breathe deeply, straighten their back, and avoid a kyphotic posture;
  5. the regularity of exercises is important (optimally – daily), since after the cessation of exercise, their positive effect is quickly lost.

After 3 weeks and for the next 3 months, patients with fractures of the vertebral bodies should follow the regime of “intermittent” rest in a horizontal position”: after 2 hours of staying in a vertical position, it is necessary to spend 20 minutes in the “lying” position [26, 27]. Chiropractic is strictly prohibited, but there is one study to date that suggests a multimodal approach, linking gentle manual therapy to exercise. The authors demonstrated the effectiveness of the program in reducing pain and improving the physical function and endurance of the back muscles in patients with pain syndrome due to fracture of the vertebral bodies [28]. However, no one has yet confirmed these recommendations; there are many complications in the form of new fractures of the vertebral bodies after manual therapy.

Treatment of chronic pain in osteoporosis complicated by vertebral fractures

About 66% of women with osteoporosis complicated by vertebral compression fractures suffer from chronic back pain, with 26% experiencing daily pain lasting more than 10 hours. Chronic pain syndrome is associated with incorrect or complete lack of treatment of vertebral fractures in the acute period [29]. In this case, the stimulation of pain receptors becomes not only a fracture of the trabeculae, but their stretching and compression. The pain syndrome is aggravated by myofascial disorders, changes in disco-body relationships and the development of biomechanics disorders due to spinal column deformities. Chronic pain in fractures of the vertebral bodies forms phobias in patients with osteoporosis.

NSAID courses are recommended for chronic pain relief (in the absence of contraindications from the gastrointestinal tract) [30], but they have a negative effect on bone metabolism, so their use cannot be long-term [31].

Analgesics in the form of applications of preparations with dimexide (dimexide 10%-10.0 + novocaine 0.5%-5.0 + diphenhydramine 1%-1.0 + Vit-B12 250 mcg + diclonac 3.0) on the area of ​​pain projection on the 4-6 hours 5-6 procedures; Reflexology (acupuncture, electropuncture, laser puncture). For the relief of myalgia, courses of sirdalud are recommended (2-4 mg 1-2 times a day, 7-10 days [32]. In case of pathological vertebral fractures against the background of osteoporosis due to concomitant diseases, physiotherapy is possible only in 10-15% of patients [33] There are no convincing data on the possibility of using radiofrequency denervation of the medial branches of the dorsal arches innervating the facet joint in osteoporosis to relieve chronic pain.

Depression and sleep disturbance in patients with chronic pain from vertebral fractures due to osteoporosis require antidepressants and psychological assistance. To reduce the psychological problems associated with chronic pain syndrome, various educational programs for patients with self-control training are used [34]. Chronic pain is facilitated by the constant wearing of corsets (except for sleep) [12], which unload the spine by restoring the “balloon” function of the abdominal cavity and, by increasing intra-abdominal pressure, unload the spine. Soft and semi-rigid constructions do not cause atrophy of the muscular “corset”.

CONCLUSION

The likelihood of developing chronic pain syndrome can be reduced with the timely administration of therapy aimed at treating osteoporosis, the purpose of which is primarily to prevent new fractures and all those deformities of the body that lead to the formation of pain syndrome. Fundamental in the treatment of pathological fractures of the vertebral bodies, complicating the course of osteoporosis, is the appointment of pathogenetic drugs for the treatment of osteoporosis (bisphosphonates, denosumab, teriparatide) with adequate replenishment of the intake of calcium salts and relief of deficiency or insufficiency of vitamin D.

Patients with a long-term pain syndrome that is not relieved by complex conservative treatment may be candidates for such a minimally invasive intervention as vertebroplasty followed by pathogenetic therapy for osteoporosis, aimed primarily at preventing new skeletal fractures.

ADDITIONAL INFORMATION

Conflict of interest . The authors declare the absence of obvious and potential conflicts of interest related to the publication of this article.

1. Griffith JF. Identifying osteoporotic vertebral fracture. Quant Imaging Med Surg. 2015;5(4):592-602. doi: 10.3978/j.issn.2223-4292.2015.08.01

2. Jimenez-Andrade JM, Mantyh WG, Bloom AP, et al. The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain. Neurobiol Aging. 2012;33(5):921-932. doi: 10.1016/j.neurobiolaging.2010.08.008

3. Wu SS, Lachmann E, Nagler W. Current Medical, Rehabilitation, and Surgical Management of Vertebral Compression Fractures. J Women’s Health. 2003;12(1):17-26. doi:10.1089/154099903321154103

4. Sinaki M, Pfeifer M, Preisinger E, et al. The Role of Exercise in the Treatment of Osteoporosis. Current Osteoporosis Reports. 2010;8(3):138-144. doi: 10.1007/s11914-010-0019-y

5. Dreyfuss P, Tibiletti C, Dreyer SJ. Thoracic zygapophyseal joint pain patterns. A study in volunteer normals. Spine (Phila Pa 1976). 1994;19(7):807-811.

6. Francis RM, Aspray TJ, Hide G, et al. Back pain in osteoporotic vertebral fractures. Osteoporos Int. 2007;19(7):895-903. doi: 10.1007/s00198-007-0530-x

7. Gasik R, Styczyński T. Specifics of pharmacological treatment of back pains in people of old age. Polski Merkuliusz lekarski 2006; 21(124):394-397

8. Watts NB, Adler RA, Bilezikian JP, et al. Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline. J Clin Endocr Metab. 2012;97(6):1802-1822. doi: 10.1210/jc.2011-3045

9. Melnichenko G.A., Belaya Zh.E., Rozhinskaya L.Ya. osteopathy. – 2016. – V. 19. – No. 3. – C. 28-36. [Melnichenko GA, Belaya ZE, Rozhinskaya LY, et al. Summary of Clinical Guidelines for the Diagnosis and Treatment of Osteoporosis of the Russian Association of Endocrinologists. Osteoporosis and osteopathy. 2016;19(3):28-36. (In Russ.)] doi: 10.14341/osteo2016328-36

10. Chosa K, Naito A, Awai K. Newly developed compression fractures after percutaneous vertebroplasty: comparison with conservative treatment. Japanese Journal of Radiology. 2011;29(5):335-341. doi:10.1007/s11604-011-0564-z

11. Ensrud KE, Schousboe JT. Vertebral Fractures. N Engl J Med. 2011;364(17):1634-1642. doi: 10.1056/NEJMcp1009697

12. Longo UG, Loppini M, Denaro L, et al. Osteoporotic vertebral fractures: current concepts of conservative care. Br Med Bull. 2011;102(1):171-189. doi: 10.1093/bmb/ldr048

13. 13. 1. Barker KL, Javaid MK, Newman M, et al. Physiotherapy Rehabilitation for Osteoporotic Vertebral Fracture (PROVE): study protocol for a randomized controlled trial. trials. 2014;15(1):22. doi: 10.1186/1745-6215-15-22

14. Denaro V, Longo UG, Denaro L. Vertebroplasty versus conservative treatment for vertebral fractures. The Lancet. 2010;376(9758):2071. doi: 10.1016/s0140-6736(10)62289-1

15. Longo UG, Loppini M, Denaro L, et al. Conservative management of patients with an osteoporotic vertebral fracture: A review of the literature. The Bone & Joint Journal. 2012;94-B(2):152-157. doi: 10.1302/0301-620x.94b2.26894

16. Vorlat P, Leirs G, Tajdar F, et al. Predictors of Recovery After Conservative Treatment of AO-Type A Thoracolumbar Spine Fractures Without Neurological Deficit. Spine. 2010:1. doi: 10.1097/BRS.0b013e3181cdb5fc

17. Park Y-S, Kim H-S. Prevention and Treatment of Multiple Osteoporotic Compression Fracture. Asian Spine Journal. 2014;8(3):382. doi: 10.4184/asj.2014.8.3.382

18. van Tulder M, Becker A, Bekkering T, et al. Chapter 3 European guidelines for the management of acute nonspecific low back pain in primary care. Eur Spine J. 2006;15(S2):s169-s191. doi: 10.1007/s00586-006-1071-2

19. Rzewuska M, Ferreira M, McLachlan AJ, et al. The efficacy of conservative treatment of osteoporotic compression fractures on acute pain relief: a systematic review with meta-analysis. Eur Spine J. 2015;24(4):702-714. doi: 10.1007/s00586-015-3821-5

20. Pfeifer M, Begerow B, Minne HW. Effects of a New Spinal Orthosis on Posture, Trunk Strength, and Quality of Life in Women with Postmenopausal Osteoporosis. Am J Phys Med Rehabil. 2004;83(3):177-186. doi: 10.1097/01.phm.0000113403.16617.93

21. Frost HM. Personal Experience in Managing Acute Compression Fractures, their Aftermath, and the Bone Pain Syndrome, in Osteoporosis. Osteoporos Int. 1998;8(1):13-15. doi: 10.1007/s001980050042

22. Bonner Jr FJ, Sinaki M, Grabois M, et al. Health Professional’s Guide to Rehabilitation of the Patient with Osteoporosis. Osteoporos Int. 2003;14(0):1-22. doi:10.1007/s00198-002-1308-9

23. Burke TN, França FJR, Meneses SRFd, et al. Postural control in elderly women with osteoporosis: comparison of balance, strengthening and stretching exercises. A randomized controlled trial. Clinic Rehabil. 2012;26(11):1021-1031. doi: 10.1177/0269215512442204

24. Yoo J-H, Moon S-H, Ha Y-C, et al. Osteoporotic Fracture: 2015 Position Statement of the Korean Society for Bone and Mineral Research. Journal of Bone Metabolism. 2015;22(4):175. doi: 10.11005/jbm.2015.22.4.175

25. Sinaki M. Yoga Spinal Flexion Positions and Vertebral Compression Fracture in Osteopenia or Osteoporosis of Spine: Case Series. Pain practice. 2013;13(1):68-75. doi: 10.1111/j.1533-2500.2012.00545.x

26. Hongo M, Miyakoshi N, Shimada Y, Sinaki M. Association of spinal curve deformity and back extensor strength in elderly women with osteoporosis in Japan and the United States. Osteoporos Int. 2011;23(3):1029-1034. doi: 10.1007/s00198-011-1624-z

27. Angın E, Erden Z, Can F. The effects of clinical pilates exercises on bone mineral density, physical performance and quality of life of women with postmenopausal osteoporosis. J Back Musculoskeletal Rehabil. 2015;28(4):849-858. doi: 10.3233/bmr-150604

28. Bennell KL, Matthews B, Greig A, et al. Effects of an exercise and manual therapy program on physical impairments, function and quality-of-life in people with osteoporotic vertebral fracture: a randomised, single-blind controlled pilot trial. BMC Musculoskel Disord. 2010;11(1). doi: 10.1186/1471-2474-11-36

29. Bianchi M, Orsini M, Saraifoger S, et al. Health and Quality of Life Outcomes. 2005;3(1):78. doi: 10.1186/1477-7525-3-78

30. Bavry AA, Khaliq A, Gong Y, et al. Harmful Effects of NSAIDs among Patients with Hypertension and Coronary Artery Disease. The American Journal of Medicine. 2011;124(7):614-620. doi: 10.1016/j.amjmed.2011.02.025

31. Vestergaard P, Hermann P, Jensen JEB, et al. Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention Study (DOPS). Osteoporos Int. 2011;23(4):1255-1265. doi:10.1007/s00198-011-1692-0

32. Vellucci R, Mediati RD, Ballerini G. Use of opioids for treatment of osteoporotic pain. Clinical Cases in Mineral and Bone Metabolism. 2014;11(3):173-176.

33. Huang LQ, He HC, He CQ, et al. Clinical update of pulsed electromagnetic fields on osteoporosis.