Effects of prefracture irradiation on the biomechanical parameters of fracture healing

This study examined the effects on the biomechanical parameters of fracture healing of a single dose of 900 rad (the approximate single-dose equivalent of 2,500 rad in 10 divided doses), given 1 day prior to closed fracture of the femur. The femurs were recovered at 2, 3, 4, 8, and 16 weeks after fracture and were mounted and tested to failure in torsion; the results were compared with those in nonirradiated controls from a previously published study. Prefracture irradiation delayed the progressive increase in biomechanical parameters of fracture healing. The delay was statistically significant up to 8 weeks after fracture. At 4 weeks, the normalized torque was 44% that of intact bone in the treated group compared with 75% for the control group. Sixteen weeks after fracture, the biomechanical and histological parameters of fracture healing of the irradiated femurs were no different from those of the nonirradiated controls. Within the treated group, the irradiated fractures remained significantly weaker than their contralateral intact bone at all time intervals, with a torque of only 79% that of intact bone at 16 weeks. Thus, femoral fractures in rats healed (or regained substantial strength) following palliative doses of radiation delivered 1 day prior to injury, but the repair process was delayed compared with that of nonirradiated controls.     

Postfracture irradiation effects on the biomechanical and histologic parameters of fracture healing

The effects of single-dose local irradiation on the biomechanical properties of closed femoral fractures were studied in 75 mature Sprague-Dawley rats. Ten days after fracture, the rats were irradiated with 900 rads at 250 kV to the entire fractured femur. At 2, 3, 4, 8, and 16 weeks after fracture, both fractured and contralateral intact femurs were recovered and evaluated biomechanically by testing to failure in torsion. Results were compared with those from a similar study involving fractures irradiated 3 days after fracture as well as nonirradiated control fractures. Fracture healing progressed faster when irradiation was delayed 10 days than when delayed 3 days, and control fractures healed more rapidly than after either delay. In the 10-day delay group, fractures showed greater strength than did those in the 3-day delay group at 8 weeks, but the strength of irradiated fractures in both groups was similarly depressed at 16 weeks, with a maximum torque well below that of control fractures. These results suggest that delaying radiation exposure of a fracture may mitigate short-term deleterious effects on fracture repair, but that long-term results may be similar to those associated with expeditious irradiation.     

Radiation-induced alterations of fracture healing biomechanics

The effects of irradiation on the normal temporal progression of the physical properties of healing fractures were studied in a rat model. Fractures were surgically produced in the femur, stabilized with an intramedullary pin, and irradiated. One group of rats was exposed to 2,500 rads in divided doses over 2 weeks, beginning 3 days after fracture, and compared to a control group with fractures which were not irradiated. Animals were sacrificed at periodic intervals and the bones were tested to failure in torsion. The torque, stiffness, and energy increased and the angle decreased for the nonirradiated specimens in the expected fashion. This progression was deleteriously altered in the irradiated femurs.     

Comparison of healing process in open osteotomy model and closed fracture model

OBJECTIVE: Comparison of the healing process in open osteotomy and closed fracture models that were used to study fracture healing. DESIGN: Randomized, prospective study in experimental animals, with a recovery duration of two and four weeks. SETTING: Unrestricted cage activity with weight bearing as tolerated. ANIMALS: Thirty-four skeletally mature, female New Zealand White rabbits. INTERVENTIONS: Closed fractures and open osteotomies of the tibial diaphysis were reduced and immobilized with four-pin, double-bar external fixators. MAIN OUTCOME MEASUREMENTS: Callus circumference was measured with a tape measure, bridging callus was assessed on biplane radiographs and evaluated histologically, and torsional stiffness and maximum torque were measured. RESULTS: Periosteum damage was more severe and hematoma formation was smaller in the osteotomy model, resulting in a delay in biological healing and restoration of the biomechanical properties. CONCLUSIONS: Investigators should consider the difference between the closed fracture and open osteotomy models when selecting an animal model to investigate fracture healing.     

Neuromuscular electrical stimulation enhances fracture healing: results of an animal model.

Neuromuscular electrical stimulation (NMES) could simulate physiological muscle functions known to be associated with the normal bone healing process. The object of the present study was to evaluate the effect of NMES on fracture healing, using an animal model. Thirty rabbits received unilateral, transverse, mid-tibial, 3-mm gapped osteotomies that were stabilized with double-bar external fixators. The femoral vein was ligated to induce venous stasis. From the fourth post-operative day, the study group was treated with 1 h daily of NMES for four weeks, while the control group was treated without NMES. For NMES, two surface electrodes were used: one above the patellar tendon and another around the lateral thigh. Callus area and mineral content at the osteotomy gap were measured, biweekly, using computerized tomographic examinations. Biomechanical properties of healing were evaluated with a torsion test, eight weeks after the index operation. Osteotomies treated with NMES exhibited 31% (p=0.01) higher mineral content and 27% (p=0.009) larger callus area than control osteotomies at eight weeks. The maximum torque, torsional stiffness, angular displacement at maximum torque, and energy required to failure of specimens in the study group were 62% (p=0.006), 29% (p=0.03), 34.6% (p=0.008), and 124% (p<0.0001) higher, respectively, than those in the control group at eight weeks. The results of the present study demonstrated that the use of NMES can enhance callus development and mineralization, with the consequent improvement in biomechanical properties of the healing bone.     

Effect of low molecular weight heparin on fracture healing in a stabilized rat femur fracture model.

The purpose of this study was to evaluate the effect of low molecular weight heparin (LMWH) on fracture healing in a standard stabilized rat femur fracture model. A closed, mid-diaphyseal transverse fracture was created in the right femur of Long-Evans rats after insertion of a 0.8-mm K-wire into the medullary canal. Animals were randomized to receive either LMWH (70 units/kg dalteparin) or an injection of normal saline daily for 2 weeks. Animals were sacrificed at 2, 3, and 6 weeks. Fracture healing was assessed by radiographs, histology, and mechanical testing. There were no significant differences between the control and LMWH groups in the percentage of animals with radiographic bridging callus at each time point. Histologic appearance of fracture healing was similar between the control and LMWH groups. There were no significant differences in the normalized mechanical properties of the control and LMWH groups at 2 and 3 weeks. At 6 weeks, the percent torque of the LMWH group was significantly greater than the control group ( p = 0.0072), however, there was no significant difference in the stiffness and energy absorption. Dalteparin, at the dosage used in this study, did not impair fracture healing in this standard stabilized rat femur fracture model.     

Biomechanical evaluation of early fracture healing in normal and diabetic rats.

Diabetes mellitus has been shown to alter the properties of bone and impair fracture healing in both humans and animals. The objective of this study was to document changes in the structural and material properties of intact bone and bone with healed fractures in diabetic rats compared with nondiabetic controls after 3 and 4 weeks of healing. Rods were inserted in the right femurs of control rats and rats with streptozotocin-induced diabetes, and the femurs were fractured in a standardized procedure and then allowed to heal for 3 and 4 weeks. After death, all femurs were mechanically tested to failure in torsion. The degree of healing was quantified for each animal by normalizing mechanical parameters for the femur with a healed fracture with those for the intact contralateral femur. At both time points of healing, diabetic rats exhibited inferior healing compared with that of control animals in terms of failure torque, failure stress, structural stiffness, and material stiffness of the femur with the healed fracture relative to the intact contralateral femur (p < 0.05). Our results demonstrate that the recovery of structural and material strength in femurs with healed fractures in diabetic rats is delayed by at least 1 week compared with that in controls.     

Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats

BACKGROUND: With osteoporosis emerged as one of the most important health issues, more and more investigations are focusing on osteoporotic fracture healing. However, there are few studies on the changes of microstructure and mineralized tissue of newly formed callus. OBJECTIVE: We established an osteoporotic fracture rat model to evaluate the changes of microstructure and mineralized tissue during osteoporotic fracture healing. MATERIALS AND METHODS: A mid-shaft femur fracture model was established 12 weeks after ovariectomy as an osteoporotic fracture group (OPF group). Femurs were then harvested at 4 weeks, 8 weeks and 12 weeks after fracture for peripheral quantitative computed tomography (pQCT), micro-computed tomography (MicroCT), histology and biomechanical test. A sham-operated group was used for comparison, i.e. the normal fracture group (NF group). RESULTS: The pQCT-derived total external callus area in the OPF group was smaller than that in the NF group at 4 weeks after fracture (P<0.05), whereas it was 21% larger in the OPF group than that in the NF group at 12 weeks after fracture (P<0.01). The pQCT-derived bone mineral density in the OPF group was significantly inferior to the NF group at all the time points (P<0.05 for all the time points, respectively). MicroCT data, at 12 weeks after fracture, showed the total callus, bony callus, and newly formed bone was approximately 20% lower in the OPF group than that in the NP group, and the total connectivity was 56% lower in the OPF group as compared to the NF group. Biomechanical test data, at 12 weeks after fracture, showed that the failure load of the left femur of OPF group was 17% less compared to that of the NF group (P<0.01), and 15% lower bending stiffness (P<0.05), 20% lower bending stress (P<0.01), and 28% lower energy at failure (P<0.01) were observed in the OPF group as compared to the NF group. CONCLUSION: The decrease in mineralized tissue and the not well connected microstructure in newly formed callus may explain the decline of mechanical impairment of fracture healing in the ovariectomized rats.     

The effect of aging on fracture healing in the rat

Summary The effect of age on the biomechanical properties of healing tibial fractures was studied by comparing the fracture healing in 2-year-old male Wistar rats with the fracture healing in 3-month-old male Wistar rats after 40 and 80 days of healing. There were no significant differences in the mechanical parameters after 40 days of healing, but after 80 days, a considerable delay in the fracture healing process was noted in the old rats compared with the young adult rats when evaluated by maximum load, maximum stress, stiffness, and energy absorption in a three-point bending procedure. In the contralateral, nonfractured bones, the tibiae from the old animals sustained higher loads and had higher stiffness than the bones from the young adult animals, but stress values, elastic modulus, and capacity for energy absorption was much lower in the old animals.     

The biomechanical effect of high-pressure irrigation on diaphyseal fracture healing in vivo

OBJECTIVES: To evaluate the effect of both high-pressure pulsatile lavage and bulb syringe irrigation on the biomechanical parameters of fracture healing using an in vivo open noncontaminated diaphyseal femoral fracture model in rats. BACKGROUND: The utility of high-pressure pulsatile lavage irrigation on soft tissue debridement has been extrapolated to a similar perceived benefit in the debridement of bone. However, there have been several reports of a possible deleterious effect that high-pressure pulsatile lavage may have on bone architecture, intramedullary bacterial and contaminant seeding, and fracture healing. Although a previous in vivo histologic study suggests damage to bone architecture and impairment of early bone formation, it remains unclear whether these microscopic findings translate to a detectable decline in the biomechanical strength of the healing fracture. To our knowledge, there have been no reports of the in vivo effects high-pressure pulsatile lavage on fracture healing in open diaphyseal fractures. MATERIALS AND METHODS: Using sterile technique, standard open transverse mid-shaft femur fractures were created in thirty-six rats randomized into three groups: a control group underwent retrograde intramedullary pinning only; a bulb syringe irrigation group and a high-pressure pulsatile lavage group underwent identical procedures as the control group, except that the osteotomy site was irrigated with bulb syringe irrigation and high-pressure pulsatile lavage, respectively, before insertion of the intramedullary pin. Six rats from each group were killed at three weeks and six weeks, and the femora was mechanically tested in bending. RESULTS: Mechanical testing of the thirty-six femora revealed that the peak bending force (17.7 +/- 10.2 N) and stiffness (21.2 +/- 5.1 N/mm) of the healing fracture in the high-pressure irrigation group were significantly lower at three weeks when compared with the control (peak force, 28.1 +/- 5.9 N; stiffness, 31.4 +/- 5.8 N/mm) and the bulb syringe (peak force, 27.7 +/- 3.3 N; stiffness, 23.6 +/- 4.5 N/mm) irrigation groups (p < 0.05). The 37 percent lower peak bending force and 32 percent lower stiffness in the high-pressure pulsatile lavage group after three weeks of fracture healing were not present in the femora tested at six weeks. The high-pressure pulsatile lavage group did reveal a trend toward a lower peak bending force and stiffness after six weeks of fracture healing when compared with the control and bulb syringe irrigation groups, but the differences were not statistically significant at the 95 percent level. CONCLUSIONS: The use of high-pressure pulsatile lavage in open noncontaminated diaphyseal femur fractures in rats has a significant negative impact on the mechanical strength of the fracture callous during the early phases (three weeks) of fracture healing. However, it appears that the early deleterious effect of high-pressure pulsatile irrigation is not apparent in the late phases (six weeks) of fracture healing. Further study is required to evaluate the effect of high-pressure pulsatile lavage on fracture healing in the presence of wound contamination, fracture comminution, and soft tissue damage. CLINICAL SIGNIFICANCE: The findings of this study suggest that selective use of high-pressure irrigation in the management of open fractures appears warranted. In situations in which high-pressure lavage may be deleterious to bone healing, alternative strategies that optimize bacterial removal from soft tissues while preserving bone architecture will need to be investigated.     

Dsteoporosis influences the middle and late periods of racture healing in a rat osteoporotic model

OBJECTIVE: To evaluate the influence of osteoporosis on the middle and late periods of fracture healing process through observing the histomorphological changes, bone mineral density and biomechanical properties in ovariectomized rats. METHODS: Eighty-four female SD rats of 4 months old were randomly divided into osteoporosis group and sham operation group, 42 in each. Rats in osteoporosis group were performed ovariectomy operation while those in sham operation group were given sham operation. A midshaft tibia fracture model was established 10 weeks after ovariectomy. Tibias were harvested 2, 4, 6, 12, 18 weeks after fracture for bone mineral density, histomorphological and biomechanical evaluation. RESULTS: Compared with the sham operation group, callus bone mineral density was 12.8%, 18.0%, 17.0% lower in osteoporosis group 6, 12, 18 weeks after fracture, respectively (P<0.05); callus failure load was 24.3%, 31.5%, 26.6%, 28.8% lower in osteoporosis group, and callus failure stress was 23.9%, 33.6%, 19.1%, 24.9% lower in osteoporosis group 4, 6, 12, 18 weeks after fracture, respectively (P<0.05). In osteoporosis group, endochondral bone formation was delayed, more osteoclast cells could be seen around the trabecula, and the new bone trabecula arranged loosely and irregularly. CONCLUSIONS: Osteoporosis influences the middle and late periods of fracture healing in the rat osteoporotic model. The impairment is considered to be the result of combined effects of prolonged endochondral calcification, high activated osteoclast cell and the deceleration of the increase in bone mineral density.     

Osteoporosis influences the middle and late periods of fracture healing in a rat osteoporotic model

Osteoporosisischaracterizedbydecreasedbonemass, increasedbonefragilityinducedbydemolitionofbonemicrostructureandincreasedsusceptibilitytofracture. Currentstudiesmainlyfocusonthepreventionoffracture. However, theinfluenceofosteoporosisonthefracturehealingremainspoorlyunderstoodandcontroversial.Inourpreviousstudy, wehaveevaluatedtheeffectofosteoporosisontheearlyperiodoffracturehealing, andfoundthatosteoporosisinfluencesthequantityandqualityofcallusduringtheearlyperiodofracturehealing.1 Incurrent…     

Osteoporosis influences the early period of fracture healing in a rat osteoporotic model

Osteoporotic fractures commonly occur in the elderly. Although current therapies are aimed at the prevention and treatment of osteoporotic fractures, studies examing the fracture healing process in osteoporotic bone are limited. We produced an osteoporotic rat model by ovariectomy (ovx) and maintained a low calcium diet (LCD) in order to evaluate the influence of osteoporosis on fracture healing. Callus formation and strength was monitored over a 3 week period by histological and biomechanical assessment. Data collected simultaneously on a group of rats undergoing sham surgery (sx) were used for comparison. A 40% reduction in fracture callus cross-sectional area and a 23% reduction in bone mineral density in the healing femur of the ovx rats was observed on day 21 following fracture as compared with the sx group (p < 0.01). Biomechanical data from the healing femur of the ovx rats revealed a fivefold decrease in the energy required to break the fracture callus, a threefold decrease in peak failure load, a twofold decrease in stiffness and a threefold decrease in stress as compared with the sx group (p < 0.01, respectively). Histomorphological analysis revealed a delay in fracture callus healing with poor development of mature bone in the ovx rats. This study provides physical evidence of altered fracture healing in osteoporotic bone, which may have important implications in evaluating the effects of new treatments for osteoporosis on fracture healing.     

Effect of recombinant human osteogenic protein-1 on the healing of a freshly closed diaphyseal fracture

Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.     

Mechanical strength of fracture callus in osteopenic bone at different phases of healing

OBJECTIVES: To quantify and compare peak bending force and stiffness of fractured femurs during healing of ovariectomized (OVX) and sham-operated (SHAM) rats. DESIGN: Temporal biomechanical animal study. SETTING: Rat femurs were fractured and surgically fixed by a qualified surgeon. The inherent instability of the fixation system employed produced delayed union of the fracture. All biomechanical assessments were performed with servohydraulic test machines (Instron Inc., Canton, MA, U.S.A.; and MTS Corp., Eden Prairie, MN, U.S.A.). INTERVENTION: OVX was performed sixteen weeks before femur fracture, and the effect of OVX on healing fractures was determined. MAIN OUTCOMES: Peak bending force and stiffness of the healing femurs at four, six, and eight weeks after fracture. RESULTS: Peak bending loads of the healing fractured femurs in the OVX and SHAM animals were not significantly different. Peak bending loads for the OVX animals at four and six weeks were significantly lower than the peak load at eight weeks (p < 0.05), whereas no difference was found in the peak load with respect to time for the SHAM animals. Both SHAM and OVX animals had greater bending stiffness of the healing fractured femur after eight weeks of healing than at four weeks (p < 0.05). CONCLUSIONS: OVX is known to reduce cancellous bone mass and strength, but the effect of OVX on healing of fractures in cortical bone is controversial. This study, using a delayed-union model, found no significant differences between OVX and SHAM animals in the breaking strength of healing fractures.     

Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model

A randomised, blinded, prospective animal study with 296 male C57BL/6N mice was performed to evaluate the biomechanical, biomolecular, biochemical, and histological impact of anti-inflammatory medications on fracture healing. A reproducible closed tibia fracture was created and stabilised with an intramedullary pin. Animals were randomised to placebo, ketorolac, ibuprofen, celecoxib, or rofecoxib treatment groups with biomechanical and biochemical testing at 4, 8, and 12 weeks. A second arm of the study was conducted in which animals were randomised to indomethacin or placebo treatment with biomechanical testing at 12 weeks. Histological and biomolecular studies were performed at 2 weeks on all groups in the first arm of the study. Biomechanical testing consisted of three-point bending evaluating maximum load, energy absorbed to maximum load, and stiffness. Safranin O-Fast Green stain was performed for histology. Biochemical quantifications of chondroitin and dermatan sulphate, hydroxyproline, total protein, and DNA content were performed. Osteocalcin and collagen types II and X were evaluated by in situ hybridisation. Some mechanical differences were seen between ketorolac and placebo at 4 weeks with respect to energy absorbed, but there were no differences in maximum load or stiffness seen between any treatment group and placebo at any time point. Indomethacin, celecoxib, rofecoxib, ibuprofen, and ketorolac did not significantly affect fracture healing in this young murine model.     

Prediction of mechanical properties of healing fractures using acoustic emission.

The objective of this study was to develop a non-destructive method for monitoring fracture healing with acoustic emission (AE). Experimentally produced fractures of the rat femur were tested in tension and in torsion at 4, 6, 8 and 12 weeks after fracture. AE signals were monitored during these mechanical tests. The values for load and torque at the initiation of the AE signal were defined as new mechanical parameters. The apparent density and ash density of the fracture site were also measured at each time period. Tensile strength, tensile stiffness, maximum torque and torsional stiffness of the fracture site increased with time. The AE signal was detected before complete specimen failure. Load and torque for initiation of AE increased proportionally with increasing mechanical properties. The mineral density, however, reached a plateau at 8 weeks, when callus mechanical strength was approximately 50% of control. Load for initiation of AE was strongly correlated with the strength (r = 0.98), stiffness (r = 0.88), and failure strain (r = -0.63) of the callus. Torque for initiation of AE was highly correlated with the maximum torque (r = 0.95) and torsional stiffness (r= 0.93) of the callus. The findings of the present study indicated that some mechanical properties of healing fractures could be estimated by monitoring AE signals.     

Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model

Osteoporosis (OP) is one of the most prevalent bone diseases worldwide with bone fracture the major clinical consequence. The effect of OP on fracture repair is disputed and although it might be expected for fracture repair to be delayed in osteoporotic individuals, a definitive answer to this question still eludes us. The aim of this study was to clarify the effect of osteoporosis in a rodent fracture model. OP was induced in 3‐month‐old rats (n = 53) by ovariectomy (OVX) followed by an externally fixated, mid‐diaphyseal femoral osteotomy at 6 months (OVX group). A further 40 animals underwent a fracture at 6 months (control group). Animals were sacrificed at 1, 2, 4, 6, and 8 weeks postfracture with outcome measures of histology, biomechanical strength testing, pQCT, relative BMD, and motion detection. OVX animals had significantly lower BMD, slower fracture repair (histologically), reduced stiffness in the fractured femora (8 weeks) and strength in the contralateral femora (6 and 8 weeks), increased body weight, and decreased motion. This study has demonstrated that OVX is associated with decrease in BMD (particularly in trabecular bone) and a reduction in the mechanical properties of intact bone and healing fractures. The histological, biomechanical, and radiological measures of union suggest that OVX delayed fracture healing. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:384–393, 2008     

BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats

Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphogenetic proteins (BMPs). To investigate the influence of estrogen deficiency as well as the effect of early intervention, forty female wistar rats underwent ovarectomy (OVX) followed by low calcium diet. Ten rats underwent sham operations, followed by normal diet. After 6 weeks, a closed midshaft femoral fracture was induced. Ten animals received a systemic bisphosphonate injection, 10 injection of BMP-7 in the fracture, and 10 a combination. All then received a normal diet. After 2 weeks healing was evaluated using radiographs, CT, biomechanical testing, and histology. Radiography showed significant increase of bridging in groups treated with BMP-7. Callus volume was higher in these groups. Bending stiffness and strength were similar between OVX and sham, and not influenced by bisphosphonates. Significant increase was seen in groups treated with BMP-7. Histology was in accordance with other endpoints. Early fracture healing was not affected by estrogen deficiency. While no beneficiary effect of bisphosphonate treatment was found, injection of BMP-7 stimulated healing in ovarectomized rats.     

An internal locking plate to study intramembranous bone healing in a mouse femur fracture model

In most murine fracture models, the femur is stabilized by an intramedullary implant and heals predominantly through endochondral ossification. The aim of the present study was to establish a mouse model in which fractures heal intramembranously. Femur fractures of 16 SKH‐mice were stabilized by an internal locking plate. Femur fractures of another 16 animals were stabilized by an intramedullary screw. Bone repair was analyzed by radiographic, biomechanical, and histological methods. At 2 weeks, histological analysis showed a significantly smaller callus diameter and callus area after locking plate fixation. Cartilage formation within the callus could only be observed after screw fixation, but not after fracture stabilization with the locking plate. Radiological and biomechanical analysis after 2 and 5 weeks showed a significantly improved healing and a higher bending stiffness of fractures stabilized by the locking plate. Fractures stabilized by the locking plate healed exclusively by intramembranous ossification, which is most probably a result of the anatomical reduction and stable fixation. The fractures that healed by intramembranous ossification showed an increased stiffness compared to fractures that healed by endochondral ossification. This model may be used to study molecular mechanisms of intramembranous bone healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:397–402, 2010