Table 1 Recent clinical research investigating how traumatic brain injury (TBI) accelerates fracture healing

Fracture-only: 3

Fracture with TBI: 3

Healthy controls: 3

In the fracture with TBI group, several critical lncRNAs (including ENSG00000278905, ENSG00000240980, ENSG00000255670, and ENSG00000196634) were involved in regulating the cellular activity of basophils, cytotoxic T cells, B cells, and endothelial cells.

2021²¹⁶

TBI: 30

Femoral fracture: 30

Femoral fracture with TBI: 30

Healthy subjects: 30

Faster femoral fracture healing occurred in the femoral fracture with TBI group than in the femoral fracture-only group. BMP-2, FGF-2, IL-1β, and PDGF levels in the femoral fracture with TBI group were significantly elevated over 12 h and after 4 weeks (indicating their potential involvement in accelerated fracture healing among patients with TBI).

2021²¹⁷

Tibial fracture with TBI: 26

Simple tibial fracture: 26

TBI promoted callus formation and heterotopic ossification in patients with fracture but did not alter fracture healing time. In patients with tibial fracture and brain injury, reduced expression of miR‑433 resulted in up-regulated expression of SPP1 in calluses, heterotopic ossification tissues, and plasma.

2021²¹⁸

30 female patients:

Completely healed fracture: 10

Fracture with TBI: 10

Isolated fracture: 10

Fractures accompanied by TBI up-regulated the expression of miRNA-92a-3p in systemic circulation, inhibited IBSP levels at the fracture site, activated PI3K/AKT signaling, and accelerated the translation and transcription of osteogenic genes, thus accelerating fracture healing and callus formation.

2021²¹⁹

Fracture: 6

Non-fracture: 6

Fracture with TBI: 6

Patients with fracture and TBI had significantly lower serum miR-16-5p levels at 24 h and 72 h post-injury compared to the fracture-only patients.

2019²²⁰

Fracture: 6

Non-fracture: 6

Fracture with TBI: 6

Elevated miRNA-26a-5p may be involved in faster fracture healing in patients with TBI by inhibiting PTEN and PI3K/AKT signaling.

2019²²¹

Clavicle fracture with TBI: 22

Clavicle fracture alone: 25

Blood vessel formation was increased in patients with fracture and TBI. NGF and VEGF levels were higher in patients with fracture and TBI, as compared to patients with only fracture, contributing to shorter fracture healing time.

2018²²²

Clavicle fracture with TBI: 22

Clavicle fracture alone: 25

Increased percentages of M2 macrophages were correlated with shorter fracture healing time in patients with TBI. In addition, M2 macrophage polarization in bone regeneration was found to potentially promote bone fracture healing.

2018²²³

Long-bone fracture with TBI: 25

Long-bone fracture alone: 33

Shorter fracture healing time in patients with TBI may result from enhanced HIF-1α levels in fracture haematoma and serum.

2017²²⁴

Limb fracture with TBI: 25 males and 15 females

Simple fracture: 27 males and 13 females

TBI: 28 males and 12 females

Healthy: 24 males and 16 females

Serum NGF and EGF levels were increased in the limb fracture with TBI group and involved in promoting fracture healing.

2013²²⁵

Femoral shaft fracture with TBI: 20

Femoral shaft fracture alone: 49

TBI was correlated with faster fracture healing and elevated callus formation. TBI severity and intracranial haemorrhage type did not statistically contribute to bone healing.

2012²²⁶

Mandibular fractures with severe TBI: 24

Mandibular fractures alone: 21

Time to callus formation was positively correlated with TBI and coma duration but not with age, gender, and fracture distribution.

2012²²⁷