Bone healing

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Bone healing of a fracture by forming a callus as shown by X-ray.

Bone healing, or fracture healing, is a proliferative physiological process in which the body facilitates the repair of a bone fracture.

Generally bone fracture treatment consists of a doctor reducing (pushing) displaced bones back into place via relocation with or without anaesthetic, stabilizing their position to aid union, and then waiting for the bone's natural healing process to occur.

Adequate nutrient intake has been found to significantly affect the integrity of the fracture repair.[1] Age, Bone type, drug therapy and pre existing bone pathology are factors which affect healing. The role of bone healing is to produce new bone without a scar as seen in other tissues which would be a structural weakness or deformity.[2]

The process of the entire regeneration of the bone can depend on the angle of dislocation or fracture. While the bone formation usually spans the entire duration of the healing process, in some instances, bone marrow within the fracture has healed two or fewer weeks before the final remodeling phase.[citation needed]

While immobilization and surgery may facilitate healing, a fracture ultimately heals through physiological processes. The healing process is mainly determined by the periosteum (the connective tissue membrane covering the bone). The periosteum is one source of precursor cells which develop into chondroblasts and osteoblasts that are essential to the healing of bone. The bone marrow (when present), endosteum, small blood vessels, and fibroblasts are other sources of precursor cells.[3]

Primary healing[edit]

Primary healing (also known as direct healing) requires a correct anatomical reduction which is stable, without any gap formation. Such healing requires only the remodeling of lamellar bone, the Haversian canals and the blood vessels without the callus formation. This process may take a few months until a few years.[4]

Contact healing[edit]

When the gap between the bone ends is less than 0.01 mm, and interfragmentary strain is less than 2%, contact healing can occur. In this case, cutting cones which consists of osteoclasts are formed across the fracture lines, generating cavities at a rate of 50–100 μm/day. Osteoblasts then fill up the cavities with the Haversian system. This caused the formation of lamellar bone that oriented longitudinally along the long axis of the bone. Blood vessels are also formed that penetrate the Harversian system. Remodelling of lamellar bone resulted in fracture healing without going through the callus formation.[4]

Gap healing[edit]

In this case, the fracture gap should be less than 800 μm to 1 mm. The fracture is filled by osteoclasts and then by lamellar bone oriented perpendicular to the axis of the bone. This orientation of lamellar bone is weak, thus a secondary osteonal reconstruction is required to re-orientate the lamellar bone back to the longitudinal direction. This process takes three to eight weeks.[4]

Secondary healing[edit]

Secondary healing (also known as indirect fracture healing) is the most common form of bone healing. It usually consists of only endochondral ossification. Sometimes, intramembranous ossification may occur together with endochondral ossification. Intramembranous ossification, mediated by perisoteal layer of bone, occurs without the formation of callus. For endochondral ossification, deposition of bone only occurs after the mineralised cartilage.[5] This process of healing occurs when the fracture is treated conservatively using orthopaedic cast or immobilisation, external fixation, or internal fixation.[4]

There are three major phases of fracture healing, two of which can be further sub-divided to make a total of five phases:[5]

  • 1. Reactive phase
    • i. Fracture and inflammatory phase
    • ii. Granulation tissue formation
  • 2. Reparative phase
    • iii. Cartilage callus formation
    • iv. Lamellar bone deposition
  • 3. Remodeling phase
    • v. Remodeling to original bone contour

Reactive[edit]

After fracture, blood cells accumulates adjacent to the injury site. Soon after fracture, the blood vessels constrict, stopping any further bleeding. Within a few hours after fracture, the extravascular blood cells form a blood clot, known as a hematoma.[5] The haematoma acts as a template for callus formation. These cells including macrophages release inflammatory mediators such as cytokines (Tumor necrosis factor alpha (TNFα), Interleukin-1 family (IL-1), Interleukin 6 (IL-6), Interleukin 11 (IL-11), and Interleukin 18 (IL-18)) and increase blood capillary permeability. Inflammatory response peaks by 24 hours and completed by seven days. Through Tumor necrosis factor receptor 1 (TNFR1) and Tumor necrosis factor receptor 2, TNFα mediates the differentiation of mesenchymal stem cell (orignated from the bone marrow) into osteoblast and chondrocytes. Stromal cell-derived factor 1 (SDF-1) and CXCR4 mediates the recruitment of mesenchymal stem cells. IL-1 and IL-6 are the most important cytokines for bone healing. IL-1 promotes callus formation and formation of blood vessels. IL-6 promotes the differentiation of osteoblasts and osteoclasts.[4] All of the cells within the blood clot degenerate and die. Within this area, the fibroblasts replicate. Within 7-14 days, they form a loose aggregate of cells, interspersed with small blood vessels, known as granulation tissue.[5] Osteoclasts move in to reabsorb dead bone ends, and other necrotic tissue is removed.[6]

Reparative[edit]

Radiolucency around a 12 day old scaphoid fracture that was initially barely visible.[7]

Seven to nine days after fracture, the cells of the periosteum replicate and transform. The periosteal cells proximal to (on the near side of) the fracture gap develop into chondroblasts, which form hyaline cartilage. The periosteal cells distal to (at the far end of) the fracture gap develop into osteoblasts, which form woven bone[5] through bone resorption of calcified cartilage and recruitment of bone cells and osteoclasts.[4] The fibroblasts within the granulation tissue develop into chondroblasts which also form hyaline cartilage. These two new tissues grow in size until they unite with each other. These processes culminate in a new mass of heterogeneous tissue known as a fracture callus.[5] Callus formation peaks at Day 14 of fracture.[4] Eventually, the fracture gap is bridged.[5]

The next phase is the replacement of the hyaline cartilage and woven bone with lamellar bone. The replacement process is known as endochondral ossification with respect to the hyaline cartilage and bony substitution with respect to the woven bone. Substitution of the woven bone with lamellar bone happens before the substitution of the hyaline cartilage with lamellar bone. The lamellar bone begins forming soon after the collagen matrix of either tissue becomes mineralized.[5] At this stage, the process is induced by IL-1 and TNFα.[4] The mineralized matrix is penetrated by microvessel and numerous osteoblasts. The osteoblasts form new lamellar bone upon the recently exposed surface of the mineralized matrix. This new lamellar bone is in the form of trabecular bone. Eventually, all of the woven bone and cartilage of the original fracture callus is replaced by trabecular bone, restoring most of the bone's original strength.[5]

Remodelling[edit]

The remodelling process begins as early as three to four weeks after fracture and may 3 to 5 years to be fully completed.[4] The remodeling process substitutes the trabecular bone with compact bone. The trabecular bone is first resorbed by osteoclasts, creating a shallow resorption pit known as a "Howship's lacuna". Then osteoblasts deposit compact bone within the resorption pit. Eventually, the fracture callus is remodelled into a new shape which closely duplicates the bone's original shape and strength. This process can be achieved by the formation of electrical polarity during partial weight bearing a long bone;[5] where electropositive convex surface and electronegative concave surface activates osteoclasts and osteoblasts respectively.[4] This process can be enhanced by certain synthetic injectable biomaterials, such as cerament, which are osteoconductive and actively promote bone healing.[5]

Obstructions to Bone Healing[edit]

Femur (top) healed while improperly aligned
  1. Poor blood supply which leads to the death of the osteocytes. Bone cell death is also dependent on degree of fracture and disruption to the Haversian system.
  2. Condition of the soft tissues. Soft tissue in between bone ends restricts healing.
  3. Nutrition and drug therapy. Poor general health reduces healing rate. Drugs that impair the inflammatory response impede healing also.
  4. Infection. Diverts the inflammatory response away from healing towards fighting off the infection.
  5. Age. Young bone unites more rapidly than adult bone.
  6. Pre-existing bone malignancy.
  7. Mechanical factors such as the bone not being aligned and too much or too little movement. Excess mobility can disrupt the bridging callus, interfering with union; but slight biomechanical motion is seen to improve callus formation.[6]

Complications[edit]

Complications of fracture healing include:

  1. Infection: this is the most common complication of fractures and predominantly occurs in open fractures. Post-traumatic wound infection is the most common cause of chronic osteomyelitis in patients. Osteomyelitis can also occur following surgical fixation of a fracture.[8]
  2. Non-union: no progression of healing within six months of a fracture occurring. The fracture pieces remain separated and can be caused by infection and/or lack of blood supply (Ischaemia) to the bone.[9] There are two types of non-union, atrophic and hypertrophic. Hypertrophic involves the formation of excess callus leading to bone ends appearing sclerotic causing a radiological "Elephants Foot" appearance[6] due to excessive fracture ends mobility but adequate blood supply.[4] Atrophic non-union results in re-absorption and rounding of bone ends[6] due to inadequate blood supply and excessive mobility of the bone ends.[4]
  3. Mal-union: healing occurs but the healed bone has 'angular deformity, translation, or rotational alignment that requires surgical correction'. This is most common in long bones such as the femur.[10]
  4. Delayed union: healing times vary depending on the location of a fracture and the age of a patient. Delayed union is characterised by 'persistence of the fracture line and a scarcity or absence of callus formation' on x-ray. Healing is still occurring but at a much slower rate than normal.[9]

Gallery[edit]

Footnotes[edit]

  1. ^ Susan E. Brown, PhD. "How to Speed Fracture Healing" (PDF). Center for Better Bones. While no scientist has yet conducted a clinical trial using all 20 key nutrients for fracture healing, several studies have found multi-nutrient therapy to reduce complication and accelerate fracture healing. 
  2. ^ Gomez-Barrena E, Rosset P, Lozano D, Stanovici J, Ermthaller C, Gerbhard F. Bone fracture healing: Cell therapy in delayed unions and nonunions. Bone. 2015;70:93–101.
  3. ^ Ferretti C, Mattioli-Belmonte M. Periosteum derived stem cells for regenerative medicine proposals: Boosting current knowledge. World Journal of Stem Cells. 2014;6(3):266-277. doi:10.4252/wjsc.v6.i3.266.
  4. ^ a b c d e f g h i j k l Richard, Marsell; Thomas A, Einhorn (1 June 2012). "The biology of fracture healing". Injury. 42 (6). doi:10.1016/j.injury.2011.03.031. PMC 3105171Freely accessible. PMID 21489527. 
  5. ^ a b c d e f g h i j k Mahamutha, Affshana; JothiPriya, Saveethna (2015). "Healing Mechanism in Bone Fracture" (PDF). Journal of Pharmaceutical Sciences and Research. 7 (7): 441–442. Retrieved 28 March 2018. 
  6. ^ a b c d Nyary Tamas, Scamell BE. (2015). Principles of bone and joint injuries and their healing. Surgery(Oxford). 33 (1), p 7-14.
  7. ^ Jarraya, Mohamed; Hayashi, Daichi; Roemer, Frank W.; Crema, Michel D.; Diaz, Luis; Conlin, Jane; Marra, Monica D.; Jomaah, Nabil; Guermazi, Ali (2013). "Radiographically Occult and Subtle Fractures: A Pictorial Review". Radiology Research and Practice. 2013: 1–10. doi:10.1155/2013/370169. ISSN 2090-1941.  CC-BY 3.0
  8. ^ Rowbotham, Emma; Barron, Dominic (2009). "Radiology of fracture complications". Orthopaedics and Trauma. 23 (1): 52–60. doi:10.1016/j.mporth.2008.12.008. 
  9. ^ a b Jahagirdar, Rajeev; Scammell, Brigitte E (2008). "Principles of fracture healing and disorders of bone union". Surgery. 27 (2): 63–69. doi:10.1016/j.mpsur.2008.12.011. 
  10. ^ Chen, Andrew T; Vallier, Heather A (2016). "Noncontiguous and open fractures of the lower extremity: Epidemiology, complications, and unplanned procedures". Injury. 47 (3): 742–747. doi:10.1016/j.injury.2015.12.013. 

References[edit]

  • Brighton, Carl T. and Robert M. Hunt (1986), "Histochemical localization of calcium in the fracture callus with potassium pyroantimonate: possible role of chondrocyte mitochondrial calcium in callus calcification", Journal of Bone and Joint Surgery, 68-A (5): 703-715
  • Brighton, Carl T. and Robert M. Hunt (1991), "Early histologic and ultrastructural changes in medullary fracture callus", Journal of Bone and Joint Surgery, 73-A (6): 832-847
  • Brighton, Carl T. and Robert M. Hunt (1997), "Early histologic and ultrastructural changes in microvessels of periosteal callus", Journal of Orthopaedic Trauma, 11 (4): 244-253
  • Ham, Arthur W. and William R. Harris (1972), "Repair and transplantation of bone", The biochemistry and physiology of bone, New York: Academic Press, p. 337-399