Disease relevance of Fracture Healing

• Early stages of fracture healing and osteosarcoma cell samples exhibited extensive staining for EDA+ and EDB+ fibronectin, and high mRNA levels were found [1].
• Osteogenic effects of traumatic brain injury on experimental fracture-healing [2].
• Insulin-dependent type 1 diabetes mellitus (IDDM) has been shown to alter the properties of bone and to impair fracture-healing in both humans and animals [3].
• Clodronate was administered daily 28 days before and after an experimental tibial fracture in 35 male rats, and the effect on fracture healing and posttraumatic bone loss was studied [4].
• Calcitonin did not significantly influence the fracture healing but had a pronounced effect in preventing the osteopenia [5].

High impact information on Fracture Healing

• Treatment with pamidronate did not alter the rate of fracture healing, the growth rate, or the appearance of the growth plates [6].
• However, due to side effects, PGE2 is an unacceptable therapeutic option for fracture healing [7].
• Methotrexate reduces the bone-forming potential, with possible consequences for the success of limb-saving surgery and fracture healing [8].
• The results demonstrate the importance of proper collagen-integrin interaction in fracture healing and suggest that alpha1 integrin plays an essential role in the regulation of MSC proliferation and cartilage production [9].
• The role of TNF-alpha during fracture healing was examined in wild-type and TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice [10].

Chemical compound and disease context of Fracture Healing

• Tissue substitute materials of water and Perspex for soft tissue and aluminium and hydroxyapatite for bone have been combined into phantoms to simulate tibial fractures and have been used to assess the viability of using dual x-ray absorptiometry to quantitatively measure changes in bone density during fracture healing [11].
• CONCLUSION: There was no significant difference between biodegradable osteosynthesis materials or between biodegradable materials and titanium fixation with respect to fracture healing and postoperative complications [12].

Biological context of Fracture Healing

• A novel, non-prostanoid EP2 receptor-selective prostaglandin E2 agonist stimulates local bone formation and enhances fracture healing [13].
• In later stages of fracture healing (days 16-24), PCNA expression declined at day 16 as callus ossification and remodeling spread within the fracture site and apoptosis was the dominant cell activity with the TUNEL-positive labeling peaking at day 16 and declining sharply at day 24 [14].
• Because mice lacking Cox2 form normal skeletons, our observations indicate that fetal bone development and fracture healing are different and that COX-2 function is specifically essential for fracture healing [15].
• Accelerated up-regulation of L-Sox5, Sox6, and Sox9 by BMP-2 gene transfer during murine fracture healing [16].
• Thus far, however, effects of PTH on chondrogenesis (soft callus formation) during fracture healing have not been fully elucidated [17].

Anatomical context of Fracture Healing

• In summary, these results show that TNF-alpha participates at several functional levels, including the recruitment of mesenchymal stem, apoptosis of hypertrophic chondrocytes, and the recruitment of osteoclasts function during the postnatal endochondral repair of fracture healing [10].
• Effects of 1,25(OH)2D3 on bone tissue in the rabbit: studies on fracture healing, disuse osteoporosis, and prednisone osteoporosis [18].
• Local injection of activin promoted fracture healing in rat fibula fracture models [19].
• The ER message was present in fracture callus at levels up to 70% of that found in rat uterus, and demonstrated a transient 13-fold increase in transcription by day 14 with return to baseline by day 31 of fracture healing [20].
• Thus, patients with distal tibia fractures treated with intramedullary nailing must follow weight-bearing restrictions until significant fracture healing occurs to prevent coronal plane malalignment of the fracture [21].

Associations of Fracture Healing with chemical compounds

• Radiographic, histological, and mechanical testing determined that fracture healing failed in rats treated with COX-2-selective NSAIDs (celecoxib and rofecoxib) [15].
• To determine if COX-2 functions in fracture healing, rats were treated with COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) to stop COX-2-dependent prostaglandin production [15].
• Nitric oxide modulates fracture healing [22].
• Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats [23].
• Simvastatin improves fracture healing in mice [24].

Gene context of Fracture Healing

• In this study, we analyzed the underlying molecular mechanisms by which PTH affects fracture healing and tested the hypothesis that intermittent low-dose treatment with human PTH(1-34) can increase callus formation and mechanical strength [25].
• Transient and localized expression of bone morphogenetic protein 4 messenger RNA during fracture healing [26].
• These findings suggest that several members of the TGF-beta superfamily are actively involved in fracture healing and although they are closely related both structurally and functionally, each has a distinct temporal expression pattern and potentially unique role in fracture healing [27].
• Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing [28].
• These results show for the first time that NO is expressed during fracture healing in rats and in humans, that suppression of NOS impairs fracture healing, and that supplementation of NO can reverse the inhibition of healing produced by NOS inhibitors [22].

Analytical, diagnostic and therapeutic context of Fracture Healing

• The effect of growth hormone (GH) on secondary fracture healing and callus formation has been demonstrated in several previously investigated animal models [29].
• Previous studies successfully used a biodegradable poly(d,l-lactide) coating as a local drug delivery system of growth factors from intramedullary (IM) implants to enhance fracture healing [30].
• Northern blot analysis showed that expression of CTGF/Hcs24 mRNA was 3.9 times higher on day 2 of fracture healing than that on day 0 [31].
• Using conventional riboprobe in situ hybridization, ER transcripts were not detectable in any bone cells within sections taken from normal bone and several actively remodeling bone tissues, namely, Paget's disease, renal hyperparathyroidism, and healing fracture callus [32].
• Comparison of both patient collectives revealed significantly higher increases of serum proMMP-1, VEGF and TIMP-1 in distraction patients during the lengthening period and significantly higher serum concentrations of TIMP-2 in late fracture healing period in osteotomy patients [33].

References