two-main-types-of-bone-healing

Describe the two main types of bone healing.

One of the two methods looks a lot like bone formation. What are the implications of that similarity?

The two mechanisms of bone healing are primary bone healing and secondary bone healing, just as there are two mechanisms of skin healing: you can sew it up (primary) or it can scab (secondary).

Primary bone healing involves a direct attempt by the cortex to re-establish itself after interruption, without the formation of a fracture callus.

Just like in skin, primary healing only works when the edges are closely approximated and held there without much motion. Because such close approximation/rigid fixation is required, primary bone healing is usually seen only after surgical plating (Figure 1).

Figure 1: Plating a fracture [right] is similar to suturing a laceration in that both methods approximate the ends of the disrupted tissue, compress them and hold them together tightly. These three conditions are needed for primary healing (image modified from https://en.wikipedia.org/wiki/Internal_fixation#/media/File:X_ray_internal_fixation_leg_fracture.jpg and https://commons.wikimedia.org/wiki/File:Sutures.jpg)

Primary bone healing is explained in greater detail in this excellent review*, paraphrased here: If the gap between bone ends is less than 0.01 mm and the interfragmentary strain is less than 2%, “cutting cones” consisting of osteoclasts can cross the fracture. These cones generate cavities that are then filled by bone produced by osteoblasts at the rear of the cutting cone. This reestablishes bridges of osteons across the fracture line which then remodel into normal lamellar bone. This will result in fracture healing without the formation of periosteal callus.

Secondary bone healing occurs when the ends of the fractured bones are near enough to heal** but not perfectly opposed, or when there is some motion at the fracture site. This motion is commonly seen with cast immobilization or with the placement of an intramedullary nail or rod.

Secondary bone healing involves the classical stages of injury, hemorrhage, inflammation,and “scar” formation. In bone, the “scar” is a soft callus made of cartilage;this callus then undergoes mineralization and remodeling such that, unlike skin, the tissue ultimately can become normal tissue (without any permanent scarring) (see Figure 2).

Figure 2: A healed tibia fracture (from Radiopedia) with a large amount of fracture callus. The nail keeps the ends of the fracture near each other, but the bone is not held as rigidly as would be seen with a plate. Over time, this callus will remodel to more normal contours.

The steps of secondary bone healing are thus as follows: injury;hemorrhage/inflammation; callus formation; callus mineralization; and bone remodeling. (see Figure 3)

Figure 3 (from left to right): (1) Bone breaks; (2) Hematoma (blood clot) forms at the site of the break with migration of cells (inflammation); (3) a primary callus composed of granulation tissue, fibroblasts, and new blood vessels forms from the hematoma; (4) callus cells produce cartilage, which is eventually mineralized to form woven or lamellar (disorganized bone); (5) the woven bone remodels into normal bone.

Secondary bone healing closely resembles the normal endochondral ossification of growth and development: namely, the formation of a cartilage template which is then replaced by bone. This analogy correctly suggests that secondary bone healing can lead to the formation of essentially normal tissue.

Additional Points to Consider

The formation of normal tissue after injury without scar formation is a property that bone shares with only one other organ: the liver. Like in the liver, injury to bone can be so overwhelming that no healing takes place, but under the right circumstances (of sufficiently minimal injury) recovery leads to the regeneration of normal tissue.

Note that if the ends of the fractured bones are too far apart**, or if there is too much motion at the fracture site (strain > 10%) the fracture will not heal at all.

* The Biology Of Fracture Healing. Injury. 2011 Jun; 42(6): 551–555.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105171/

** You may be wondering what “near enough to heal” really means; that is, how far apart is too far apart? Well, we know this: The original textbook definition of a "critical-sized" defect (at least in the tibia) was displacement of >50% of the cortical diameter and >1 cm in length. This was then examined in the paper, “Critical-Sized Defect in the Tibia: Is it Critical? Results From the SPRINT Trial” by Sanders, et al [https://pubmed.ncbi.nlm.nih.gov/25233157/]. This reported that “Tibial diaphyseal defects of >1 cm and >50% cortical circumference healed without additional surgery in 47% of cases. This definition of a critical-sized defect is not "critical." However, as compared with the overall cohort of tibial fractures, patients with these bone defects had a higher rate of reoperation and worse patient-based outcomes.” So those parameters, “>50% of the cortical diameter and >1 cm in length”, are reasonable, but not fixed guidelines. (It’s also interesting to note that some biological communication between the edges of the fracture is needed. A tibia that is transected, as may be seen with an amputation, makes little if any attempt to grow bone.)