Abstract
BackgroundFracture healing is orchestrated by a specific set of events that culminates in the repair of bone and reachievement of its biomechanical properties. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the early phases of callus formation in osteoporotic patients.Methodology/Principal FindingsFifty-six patients submitted to hip replacement surgery after a low-energy hip fracture were enrolled in this study. The patients were grouped according to the time interval between fracture and surgery: bone collected within 3 days after fracture (n = 13); between the 4th and 7th day (n = 33); and after one week from the fracture (n = 10). Inflammation- and bone metabolism-related genes were assessed at the fracture site. The expression of pro-inflammatory cytokines was increased in the first days after fracture. The genes responsible for bone formation and resorption were upregulated one week after fracture. The increase in RANKL expression occurred just before that, between the 4th–7th days after fracture. Sclerostin expression diminished during the first days after fracture.ConclusionsThe expression of inflammation-related genes, especially IL-6, is highest at the very first days after fracture but from day 4 onwards there is a shift towards bone remodeling genes, suggesting that the inflammatory phase triggers bone healing. We propose that an initial inflammatory stimulus and a decrease in sclerostin-related effects are the key components in fracture healing. In osteoporotic patients, cellular machinery seems to adequately react to the inflammatory stimulus, therefore local promotion of these events might constitute a promising medical intervention to accelerate fracture healing.
Highlights
The management of fragility fractures associated with osteoporosis is difficult due to several factors including inadequate fixation strength of implants used to stabilize the fracture until union of bone occurs
The expression of inflammation-related genes, especially IL-6, is highest at the very first days after fracture but from day 4 onwards there is a shift towards bone remodeling genes, suggesting that the inflammatory phase triggers bone healing
We propose that an initial inflammatory stimulus and a decrease in sclerostin-related effects are the key components in fracture healing
Summary
The management of fragility fractures associated with osteoporosis is difficult due to several factors including inadequate fixation strength of implants used to stabilize the fracture until union of bone occurs. Disturbance of the full redevelopment of mechanical strength within fracture calluses in elderly animals has been shown in experimental rat models. In another study it was described that in 6, 26 and 52 weeks old rats, there is upon aging a delay in radiographic progression of fracture healing but the expression of the key genes involved in this process is not age-dependent [1,4,5]. The fracture healing response and its temporal gene expression in elderly patients with osteoporosis has not been adequately investigated at the cellular and molecular level. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the early phases of callus formation in osteoporotic patients
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