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Normal fracture healing in long bones is a poorly defined process which to a great extent is dependent on periosteal response to injury. When this normally effective mechanism fails, electrical enhancement may prove an effective adjunct and less morbid solution than standard bone grafting procedures for periosteal reactivation.
Corrective osteotomy of the long bones may be required in patients with Paget's disease. Experiments on rabbits suggest that the safety of the procedures is of concern while the patient receives Calcitonin. Twenty-four rabbits were divided into 4 groups of 6 animals. Half of each group received maintenance doses of Calcitonin subcutaneously. In all animals the left and right ulnae were osteotomized through middiaphysis. The right ulna was fixed with a "mini" dynamic compression plate. The left ulna was not immobilized. Each group of animals was sacrificed at successive intervals of 3 weeks. Histologically, no difference was found in the healing of the fracture of test or control animals. Radiographically, the fracture line persisted longer in animals receiving Calcitonin (6 weeks vs 3 weeks). All fractures healed by 9 weeks. The fracture line disappeared more rapidly in all the immobilized bones. Based on these observations, administration of Calcitonin is not a contraindication for corrective osteotomy in Paget's disease. Osteotomies should be rigidly fixed to maintain the correction achieved surgically until healing is established.
The effect of indomethacin (2 mg/kg/day) on the healing of closed unimmobilized femoral fractures was examined in rats. A standard femoral fracture was produced in 205 male adolescent rats, and three different experiments were done. In a long-term experiment, the rats were treated with either indomethacin or placebo for 29 days and fracture healing followed for a maximum of 91 days. In two short-term experiments, the rats were treated with either indomethacin or placebo for a week and followed for a maximum of 122 days. The effect of age was studied in one experiment. Indomethacin plasma levels were about 1 microgram/ml in the indomethacin-treated animals. In the long-term experiment, indomethacin inhibited fracture healing (P less than 0.006) and increased the angulation between the femur fragments. In the short-term experiments indomethacin inhibited fracture healding (P less than 0.033) and increased the interfragmentary angle as well as fracture instability. All untreated fractures healed within 10 weeks in younger rats (210 g), whereas only 44% healed in older rats (295 g).
The effect of exogenous factor XIII on fracture healing has been tested. It could be shown that after administration of the fibrin stabilizing factor, the concentration of fibrin fibres in the fracture haematoma increases. The resistance against breaking is thus enhanced in treated animals as compared to untreated controls, mainly during the early phases of fracture healing. X-ray diagnosis demonstrated an enhanced healing process of the treated fractures. The accelerated fracture healing by factor XIII adminstration could also be substantiated through histological examinations.
In a biomechanical study, the strength of healing experimental fractures in rabbit tibias was compared for two different healing environments. During the healing period large constant compression was applied to one leg, while the other leg was subjected to cyclic compression forces. Rabbits were sacrificed at 3, 4, 5, 6, and 8 weeks after the operation. The healing bones were tested in a dynamic torsion testing machine. Results indicate that on an average basis the cyclic compression treated bones exhibited higher torque and energy absorption to failure, but lower stiffness as compared with the constant compression treated bones, during the 30 to 50 days' healing period. These differences were statistically significant. Additionally, it was estimated that a 27 per cent saving in healing time may be realized for a bone treated with cyclic as compared with constant compression.
OBJECTIVE: Although traumatic brain injury (TBI) has been clinically associated with accelerated bone healing, the factors that determine which patients experience this phenomenon remain poorly defined, and previous findings are conflicting. This study aimed to investigate the clinical factors associated with accelerated fracture healing in patients with TBI combined with comminuted fractures of the limbs, so as to provide an evidence-based foundation for elucidating the clinical phenomenon of TBI-promoted fracture healing. METHODS: A retrospective case-control study design was employed. Patients between January 2020 and April 2024 with concurrent diagnoses of TBI and comminuted fractures were included. Based on radiographic findings and RUST/mRUST scores, patients were divided into an accelerated healing group (AHG) and a normal/delayed healing group (NDHG). Clinical data including demographics (age, sex, BMI), TBI characteristics (injury site, GCS score), admission laboratory indices (blood count, coagulation function, inflammatory markers), and fracture site/local soft tissue conditions, as well as functional outcomes assessed by the Short Musculoskeletal Function Assessment (SMFA) questionnaire at final follow-up were collected. Univariate analysis and multivariate logistic regression analysis were used to identify independent factors influencing accelerated fracture healing. Receiver operating characteristic (ROC) curves were plotted to evaluate their predictive value. RESULTS: A total of 119 patients were included, with 69 in the AHG and 50 in the NDHG. Significant differences were observed between the two groups in terms of age, BMI, GCS score, and platelet count (p < 0.05). Univariate analysis showed that age, BMI, GCS score, red blood cell count, and platelet count were associated with accelerated fracture healing (p < 0.20). Multivariate logistic regression analysis indicated that younger age (OR = 0.875, 95% CI: 0.821-0.934) and lower GCS score (indicating more severe TBI; OR = 0.490, 95% CI: 0.339-0.707) were independent predictors of accelerated fracture healing. ROC curve analysis showed that the area under the curve (AUC) for age and GCS score in predicting accelerated healing were 0.893 and 0.851, respectively. CONCLUSIONS: In patients with TBI combined with comminuted fractures, younger age and greater TBI severity (lower GCS score) are independent predictors of accelerated fracture healing. These findings assist clinicians in the early identification of patients with high healing potential to optimize treatment strategies, facilitate the early identification of high-risk patients, and provide clinical clues for further exploration of the molecular mechanisms underlying neurohumoral regulation of bone regeneration.
Fracture healing was studied in 28 rabbits after their femurs had been osteomized using the carbon dioxide laser. Twenty rabbits whose femurs were osteotomized by means of a Gigli saw served as the control group. Fracture healing was initially delayed in the laser cut femurs, yet after 60 days no significant difference between the groups could be detected. The initial delay was caused by thermal damage to the laser cut bone edges. Further fragmentation of the damaged bone occurred during the immediate postoperative period.
BACKGROUND: Osteoporosis represents a salient metabolic bone disorder. Histone demethylase plays a vital role in bone development and homeostasis. This study explored the mechanism of histone demethylase KDM5A affecting osteoporotic fracture healing via the miR-495/SKP2/Runx2 axis. METHODS: The murine model of osteoporotic fracture was established. The bone mineral density, maximum elastic stress, and maximum load were tested. The relative trabecular bone volume, bone trabecular thickness, and trabecular number at the proximal end of tibia were detected. The histopathological changes of femur tissues and bone microstructure were observed. Expressions of KDM5A and osteogenic factors were detected. The cell proliferation, alkaline phosphatase activity, and calcified nodules were measured. The binding relationships between KDM5A and miR-495 promoter, and miR-495 and SKP2 were verified. The interaction between SKP2 and Runx2 was detected. The ubiquitination level of Runx2 and the stability of Runx2 protein were detected. RESULTS: KDM5A was highly expressed in the murine model of osteoporotic fracture. Interference of KDM5A expression facilitated fracture healing in osteoporotic mice. KDM5A downregulated miR-495 expression by promoting the H3K4me3 methylation of the miR-495 promoter. Inhibition of miR-495 reversed the effect of KDM5A silencing on osteoblast proliferation, differentiation, and mineralization. miR-495 facilitated osteoblast proliferation, differentiation, and mineralization by targeting SKP2. SKP2 suppressed Runx2 expression through ubiquitination degradation. Inhibition of Runx2 reversed the promoting effect of SKP2 silencing on osteogenic differentiation. CONCLUSION: KDM5A attenuated the inhibition of miR-495 on SKP2 and promoted the ubiquitination degradation of Runx2 protein by SKP2, thereby repressing osteoblast differentiation and retarding osteoporotic fracture healing.
The healing of tibial fractures was studied in 3 groups of young littermate rats; untreated osteopetrotic (ia/ia), normal littermates (ia/+) and osteopetrotic (ia/ia) cured of the disease 3 days earlier by transplanted normal spleen cells. The fracture site was completely remodeled in 4 weeks in normal rats, 6 weeks in transplanted (cured) osteopetrotic rats and 9 weeks in untreated osteopetrotic rats. The delayed healing in untreated osteopetrotic rats resulted from reduced resorption present in this mutation. Increased resorption brought about by transplantation of normal spleen cells accelerated healing in the transplanted osteopetrotic rats. Fracture repair took longer in the latter group than in normal littermates presumably because tibial fracture occurred before the 2 week interval required for skeletal transformation from osteopetrotic to normal phenotype following transplantation of normal spleen cells. These data show that alteration of the phenotype of osteopetrotic rats is reflected in fracture healing.
Fractures of the fibula were produced in rats with sciatic denervation. The denervated rats exhibited more rapid fracture healing than controls. Fifteen days following injury, enhanced union was measured by histologic assessment (p less than 0.001), and biomechanical testing including fracture stress (p less than 0.005), elastic modulus (p less than 0.005), strain at failure (p = 0.01) and energy to failure (p = 0.05).
Fracture healing is a repair process of a mechanical discontinuity loss of force transmission, and pathological mobility of bone. Through a sequence of changes of tissue development and geometry, the original structural integrity is restored. The recovery of rigidity and strength is related to tissue differentiation. In unified theory of non-operative and operative stabilized fractures, the mechanics of primary bone healing involves a complex interplay of physical and biological factors. The different patterns of bone repair respond to physical influences including strain tolerance.
The effect of hypophysectomy and hypophysectomy + testosterone treatment on fracture healing was investigated on 60 Wistar rats (30 day old). The aim of the experiment was to elucidate whether in callus formation testosterone acts directly on the cells (peripheral effect), or its effect is mediated through the hypophysis (central effect). Changes induced by hypophysectomy take place in the course of callus formation due primarily to the impairment of the enzyme system of the cells. The effect of hypophysectomy can be attenuated with testosterone which, despite hypophysectomy, stimulates fracture healing. It may be concluded that testosterone exerts a direct peripheral effect on the callus cells, presumably on their enzyme system.
Animal models demonstrated the differences in the process of fracture healing in weight-bearing and nonweight-bearing bones. Canine rib fractures regained strength properties rapidly; in canine radial fractures the return to normal stiffness levels was primary. The structural differences in fracture healing are probably functional and due more to biologic reorganization than to any measurable change in the biochemical components of the callus.
The morphologic and biochemical events during fracture callus cartilage differentiation and calcification are presented. 1. Histologic studies have demonstrated that unimmobilized fractures heal through endochondral ossification. 2. Biochemical studies have demonstrated an increase in the activities of alkaline phosphatase, enzymes involved with aerobic glucose metabolism, and lysosomal enzymes and a decrease in activities of enzymes involved with glycogen synthesis and anaerobic glycolysis. Hexosamines and hydroxyproline show a net decrease with cartilage differentiation. 3. Electron microscopic studies have demonstrated the intracellular origin and aggregation of collagen molecules, the cellular origin of matrix vesicles, and the early sites of calcification in the fracture callus.
Human growth hormone seems to improve fracture healing. Using rat experiments, the clinical experiences of other authors were reviewed critically. Examination of metabolic parameters showed no useful results. Measurement of bone length and circumference and comparison of radiographs, scintigraphs, and histologic examinations indicated positive results with regard to the improvemnt of osseous consolidation when influenced by growth hormone.
Radionuclide bone imaging was performed in a rabbit model to observe the course of fracture healing and to establish criteria for distinguishing nonunion and delayed healing from normal healing. Sequential gamma-camera images (with pinhole collimator) were collected and subjected to computer analysis. Five groups were established: a) control--immobilization; b) control--immobilization plus periosteal stripping; c) simple fracture--osteotomy; d) delayed union--osteotomy plus periosteal stripping; and e) nonunion--osteotomy, periosteal stripping and polymethyl methacrylate interposed between fracture fragments. Histographic representation of absolute count rates along rabbit tibias followed a predictable pattern in the simple-fracture and delayed-union groups. They differed only in the time of appearance of phases. The nonunion group demonstrated no recognizable sequential pattern. In this experimental model, serial bone scanning with quantitative data analysis has shown potential for indicating the course of healing in fractures and for serving as a guide to treatment.
The reaction of folic acid on fracture healing was tested on the basis of 113 rabbits. In both cases, the only application of folic acid and the combination with amino acids, the results can be regarded positively. This is also true when we consider possible methodic faults.
Do X-rays adequately reflect the strength of callus post fracture? Eleven rabbit tibiae were manually fractured and allowed to heal in plaster. At varying times post fracture, the rabbits were sacrificed and the tibiae were removed. AP and lateral X-rays of each tibia were obtained and shown to 27 orthopedists and radiologists who were asked to rank the bones in order of strength. The valid ranking was done using data obtained by loading the bones axially to failure in an Instron machine. Each physician's ranking was compared with that obtained from the Instron with a median correlation level p=0.0668. This implies that a physician, whether an orthopedist or radiologist, is not very reliable at determining early osseous union.