Orthopedic fractures are a common daily acute health issue. Improper initial management of fractures can lead to significant long-term morbidity and, potentially, mortality. With the burden of musculoskeletal disease at the forefront of health care worldwide, the World Health Organization (WHO) declared 2000-2010 the Bone and Joint Decade (BJD).  The BJD included more than 100 professional and patient organizations, with the American Academy of Orthopaedic Surgeons (AAOS) being one of the founding organizations. The campaign promoted initiatives throughout the world, with particular support for activities in developing countries. [2, 3, 4]
Since the BJD, the focus on orthopedic health has continued, with the WHO subsequently declaring a “Decade of Action for Road Safety 2011-2020,” recognizing that death and disability from traffic trauma is a major public health issue worldwide.  Orthopedic fractures are commonly seen in traffic crashes. In 2004, traffic trauma was identified by the WHO as the ninth most common cause of death worldwide, and this ranking was projected to rise if interventions were not implemented. 
In addition to those fractures sustained from daily crashes and falls, fractures are a common issue in natural disasters. For example, after the January 2013 earthquake in Haiti, the President of the AAOS at the time, Dr Joseph D Zuckerman, issued a call to arms for orthopedic health professionals to join in the relief effort and pledged the continuing support of the AAOS to the cause. 
Fractures can heal by two different mechanisms, depending on their position and stability. Primary or direct healing is possible when an anatomic reduction with compression is achieved.  With primary healing, the modeling occurs internally, and no callus is formed. Secondary or indirect healing occurs with relative stability when an anatomic reduction is not achieved or compression is not possible.  This type of healing involves the formation of a bony callus and then subsequent external remodeling to bridge the gap.
The four phases of indirect fracture healing are as follows  :
Fracture and inflammatory phase
Granulation tissue/soft callus formation
Hard callus formation, including woven bone creation 
Remodeling, including lamellar bone creation
Actual fracture injuries to the bone include insult to the bone marrow, periosteum, and local soft tissues. The most important stage in fracture healing is the inflammatory phase and subsequent hematoma formation. It is during this stage that the cellular signaling mechanisms work through chemotaxis and an inflammatory mechanism to attract the cells necessary to initiate the healing response.
Within 7 days, the body forms granulation tissue between the fracture fragments. Various biochemical signaling substances are involved in the formation of the soft callus, which lasts approximately 2 weeks.
During hard callus formation, cell proliferation and differentiation begin to produce osteoblasts and chondroblasts in the granulation tissue. The osteoblasts and chondroblasts, respectively, synthesize the extracellular organic matrices of woven bone and cartilage, and then the newly formed bone is mineralized. This stage requires 4-16 weeks.
During the fourth stage, the meshlike callus of woven bone is replaced by hard lamellar bone, which is organized parallel to the axis of the bone. This final stage involves remodeling of the bone at the site of the healing fracture by various cellular types such as osteoclasts. Remodeling can take months to years, depending on patient and fracture factors. 
Patient factors that influence fracture healing include age,  comorbidities,  medication use,  social factors,  and nutrition  (see Table 1 below). Other factors that affect fracture healing include the type of fracture,  degree of trauma,  systemic and local disease, and infection. 
Table 1. Patient Factors That Influence Fracture Healing (Open Table in a new window)
|Age ||Youth||Advanced age (>40 y)|
|Comorbidities ||None||Multiple medical comorbidities (eg, diabetes)|
|Medications ||None||Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids|
|Social factors ||Nonsmoker||Smoker|
|Nutrition [13, 17]||Well nourished||Poor nutrition|
|Fracture type ||Closed fracture, neurovascularly intact||Open fracture with poor blood supply|
|Trauma ||Single limb||Multiple traumatic injuries|
|Local factors ||No infection||Local infection|
Patients who have poor prognostic factors in terms of fracture healing are at increased risk for complications of fracture healing such as nonunion (a fracture with no possible chance of healing), malunion (healing of bone in an unacceptable position in any plane), osteomyelitis, and chronic pain.
Fractures occur when the force applied to a bone exceeds the strength of the involved bone. Both intrinsic and extrinsic factors are important with respect to fractures.  Extrinsic factors include the rate at which the bone’s mechanical load is imposed and the duration, direction, and magnitude of the forces acting on the bone. Intrinsic factors include the involved bone’s energy-absorbing capacity, modulus of elasticity, fatigue, strength, and density.
Bones can fracture as a result of direct or indirect trauma. Direct trauma consists of direct force applied to the bone; direct mechanisms include tapping fractures (eg, bumper injury), penetrating fractures (eg, gunshot wound),  and crush fractures. Indirect trauma involves forces acting at a distance from the fracture site such as tension (traction), compressive, and rotational forces.
Trauma causes more than 140,000 deaths per year in the United States, is the leading cause of death for those aged 1-34 years, and causes more years of lost productivity before age 65 years than coronary artery disease, cancer, and stroke combined.  Each year, more than 50 million Americans undergo medical treatment for an injury.  The estimated lifetime cost of these injuries is over $400 billion.
The WHO estimated that injuries account for 12% of all disability-adjusted life years (DALYs) lost, which includes a significant number of fractures.  In low- and middle-income countries, falls and traffic injuries are the top causes of disease burden, higher than communicable diseases such as tuberculosis and HIV disease. 
The proportion of burden from injury, as opposed to communicable or degenerative disease, is highest in middle-income regions such as China and South America, where it is nearing 20%.  A household survey in Sierra Leone found that 12% of respondents had experienced a traumatic injury within the preceeding year, with falls being the most common cause (40%) and the extremities being the most common site of injury. 
Fracture incidence is multifactorial and often complicated by such factors as the patient's age, sex, comorbidities, lifestyle, and occupation. In the United States, 5.6 million fractures occur each year, corresponding to a 2% incidence. 
Almost 6000 fractures were treated in an orthopedic trauma unit in Edinburgh, Scotland, in 1 year.  The overall fracture incidence in the Scottish case series was 1.13% in men and 1.16% in women. Interestingly, there was a bimodal distribution of fractures in males, with a high incidence in young men and a second rise in men starting at the age of 60 years. In women, there was a unimodal distribution of fractures, with a rise around the time of menopause.
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