Abstract
Traumatic brain injury (TBI) leads to long-term cognitive, behavioral, affective deficits, and increase neurodegenerative diseases. It is only in recent years that there is growing awareness that TBI even in its milder form poses long-term health consequences to not only the brain but to other organ systems. Also, the concept that hormonal signals and neural circuits that originate in the hypothalamus play key roles in regulating skeletal system is gaining recognition based on recent mouse genetic studies. Accordingly, many TBI patients have also presented with hormonal dysfunction, increased skeletal fragility, and increased risk of skeletal diseases. Research from animal models suggests that TBI may exacerbate the activation and inactivation of molecular pathways leading to changes in both osteogenesis and bone destruction. TBI has also been found to induce the formation of heterotopic ossification and increased callus formation at sites of muscle or fracture injury through increased vascularization and activation of systemic factors. Recent studies also suggest that the disruption of endocrine factors and neuropeptides caused by TBI may induce adverse skeletal effects. This review will discuss the long-term consequences of TBI on the skeletal system and TBI-induced signaling pathways that contribute to the formation of ectopic bone, altered fracture healing, and reduced bone mass.
Highlights
Traumatic brain injury (TBI) is the disruption of brain activity due to an external force or violent blow to the head
Recent studies suggest that the activation of the bone morphogenic protein (BMP) signaling may play a significant role in the pathogenesis of Heterotopic Ossification (HO) based on the established role for BMPs to promote de novo bone formation in non-skeletal sites [35,36,37,38]
Traumatic brain injury-induced skeletal changes seems to be dependent in part on the variations in parathyroid hormone (PTH) and vitamin D axis
Summary
Traumatic brain injury (TBI) is the disruption of brain activity due to an external force or violent blow to the head. TBI can lead to a series of physical, cognitive, social, emotional, and behavioral impairments [1] and is the leading cause of death and disability in both combat and civilian populations. More than 1.7 million people in the U.S experience a TBI annually [1], and it is a major cause of death and disability worldwide, especially in children and young adults. Many statistics do not account for individuals who have not reported an injury or received medical care, and disabilities may be significantly higher, often with long-term consequences. Individuals who have suffered mild TBI, or concussions, report adverse effects resulting from the TBI(s) months later [3] due to the rotational stress caused by head movement. This review will discuss the consequences that TBI on the skeleton and its possible mechanisms
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