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.     

有机镓促进卵巢切除大鼠骨折愈合及生长的实验研究

目的 本研究的目的 是证实有机镓对卵巢切除大鼠骨折愈合的作用.方法 40只雌性Wistar大鼠被分为2组:(1)假手术组(对照n=10只),(2)卵巢切除组(n=30只),无菌条件下腹侧入路行完整双侧卵巢摘除;假手术组摘除与卵巢重量相同的卵巢周围脂肪组织各1块.12w后对40只大鼠制造开放性骨折并予克氏针内固定.术后分为假手术组(n=10)和一个卵巢切除组(n=15)用PBS治疗,另外一个卵巢切除组(n=15)用有机镓治疗.治疗共持续4w,取骨折愈合的大鼠股骨分别进行micro-CT测定骨小梁组织结构;组织形态学测定骨组织愈合面积;生物力学测定愈合股骨的最大负荷载力;骨矿含量检测评价钙盐含量.结果 经过4w治疗,micro-CT显示有机镓治疗组平均骨小梁厚度(Tb.Th)、平均骨小梁数目(Tb.N)均明显高于对照组(P<0.05).卵巢切除组的愈合组织骨面积较假手术组降低9.2%,有机镓治疗组比卵巢切除组高34.9%(P<0.05).有机镓治疗组股骨骨折愈合强度显著高于卵巢切除组,最大负荷载力增加50.6%,结构强度增加36.5%,能量吸收增加90.9%,但是均低于假手术组.与卵巢切除组相比,有机镓治疗组显著提高愈合组织的骨矿含量.结论 有机镓能够抑制骨折后的骨量丢失,促进骨折愈合组织的生长,改善骨小梁三维结构及骨组织的力学性能,可用来促进骨质疏松性骨折的愈合并改善骨质量,预防再骨折.     

The effects of nail rigidity on fracture healing in rats with osteoporosis

Background and purpose Stress shielding from rigid internal fixation may lead to refracture after removal of the osteosynthesis material. We investigated the effect of a low-rigidity (Ti-24Nb-4Zr-7.9Sn) intramedullary nail regarding stress shielding and bone healing of osteoporotic fractures in the rat.Methods 40 female Sprague-Dawley rats, aged 3 months, were divided into the following groups: sham-operation (SHAM) (n = 10), ovariectomized (OVX) (n = 10) and OVX-fracture (n = 20). 10 SHAM rats and 10 OVX rats were killed after 12 weeks to provide biomechanical data. Ovariectomy was performed 12 weeks before fracturing both femurs in 20 rats. The left fracture was stabilized with a high-rigidity titanium alloy pin (Ti-6Al-4V; elastic modulus 110 GPa) and the right with a low-rigidity (Ti-24Nb-4Zr-7.9Sn; elastic modulus 33 GPa). The bony calluses were examined by micro-CT at 6 and 12 weeks after fracture, bone volume (BV) and total volume (TV) were determined at the callus region (ROI1) and the total femur (ROI2). Subsequently, the bones were tested mechanically by a three-point bending test.Results In the low-rigidity group, TV (ROI1) increased at 6 weeks, but BV (ROI1), BV (ROI2) were similar but maximum load increased. At 12 weeks, the maximum load and also BV (ROI1, ROI2) were increased in the low-rigidity group.Interpretation The low-rigidity nail manufactured from Ti-24Nb-4Zr-7.9Sn showed better external callus formation, seemed to reduce effects of stress shielding, and reduced bone resorption better than the stiffer nail. The low-rigidity nail was strong enough to maintain alignment of the fracture in the osteoporotic rat model without delayed union.     

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.     

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     

Influence of Age on Mechanical Properties of Healing Fractures and Intact Bones in Rats

Mechanical properties of fractured and intact femora have been studied in young and adult, male rats. A standardized, closed, mid-diaphyseal fracture was produced in the left femur, the right femur serving as control. The fracture was left to heal without immobilization. At various intervals, both fractured and intact femora were loaded in torsion until failure.

The fractured femora regained the mechanical properties of the contralateral, intact bones after about 4 weeks in young and after about 12 weeks in adult rats. For intact bones, both the ultimate torsional moment (strength) and the torsional stiffness increased with age of the animals, whereas the ultimate torsional angle remained unchanged. For bone as a material, however, the ultimate torsional stress (strength) and the modulus of rigidity (stiffness) increased with age only in young rats, being almost constant in the adult animals.

The various biomechanical parameters of the healing fractures did not reach those of the contralateral, intact bones simultaneously. The torsional moment required to twist a healing femoral fracture 20 degrees (0.35 radians), a deformation close to what an intact femur can resist, proved to be a functional and simple measure of the degree of fracture repair in rats.     

Congenital Coxa Vara and Perthes' Disease

Mechanical properties of fractured and intact femora have been studied in young and adult, male rats. A standardized, closed, mid-diaphyseal fracture was produced in the left femur, the right femur serving as control. The fracture was left to heal without immobilization. At various intervals, both fractured and intact femora were loaded in torsion until failure.

The fractured femora regained the mechanical properties of the contralateral, intact bones after about 4 weeks in young and after about 12 weeks in adult rats. For intact bones, both the ultimate torsional moment (strength) and the torsional stiffness increased with age of the animals, whereas the ultimate torsional angle remained unchanged. For bone as a material, however, the ultimate torsional stress (strength) and the modulus of rigidity (stiffness) increased with age only in young rats, being almost constant in the adult animals.

The various biomechanical parameters of the healing fractures did not reach those of the contralateral, intact bones simultaneously. The torsional moment required to twist a healing femoral fracture 20 degrees (0.35 radians), a deformation close to what an intact femur can resist, proved to be a functional and simple measure of the degree of fracture repair in rats.     

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.     

维生素K2对去卵巢大鼠股骨干骨折愈合影响的实验研究

目的探讨维生素K2能否促进卵巢切除骨质疏松(OVX)大鼠骨折愈合。方法将30只雌性大鼠随机分为3组(每组10只):假手术组(SHAM)、去卵巢组(OVX)、OVX+维生素K2组。大鼠卵巢切除术后3个月,在右侧股骨干制作单侧股骨干骨折。然后在通过维生素K2治疗8周后处死动物,行X线片检测;对骨折的股骨进行生物力学检测并观察血清骨钙素(BGLAP)、碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRACP)和雌二醇水平的变化。结果与OVX组相比,OVX+维生素K2组观察到更多骨痂组织形成和更好的骨愈合,并且BGLAP、ALP和TRACP水平降低,但是血液雌二醇水平没有观察到显著增加。与OVX组相比,OVX+维生素K2组显示出骨强度、最大负荷和弹性显著增加。结论维生素K2具有作为绝经后骨质疏松症骨折愈合新型替代治疗剂的潜力。     

The effects of nail rigidity on fracture healing in rats with osteoporosis

Background and purpose Stress shielding from rigid internal fixation may lead to refracture after removal of the osteosynthesis material. We investigated the effect of a low-rigidity (Ti-24Nb-4Zr-7.9Sn) intramedullary nail regarding stress shielding and bone healing of osteoporotic fractures in the rat.

Methods 40 female Sprague-Dawley rats, aged 3 months, were divided into the following groups: sham-operation (SHAM) (n = 10), ovariectomized (OVX) (n = 10) and OVX-fracture (n = 20). 10 SHAM rats and 10 OVX rats were killed after 12 weeks to provide biomechanical data. Ovariectomy was performed 12 weeks before fracturing both femurs in 20 rats. The left fracture was stabilized with a high-rigidity titanium alloy pin (Ti-6Al-4V; elastic modulus 110 GPa) and the right with a low-rigidity (Ti-24Nb-4Zr-7.9Sn; elastic modulus 33 GPa). The bony calluses were examined by micro-CT at 6 and 12 weeks after fracture, bone volume (BV) and total volume (TV) were determined at the callus region (ROI1) and the total femur (ROI2). Subsequently, the bones were tested mechanically by a three-point bending test.

Results In the low-rigidity group, TV (ROI1) increased at 6 weeks, but BV (ROI1), BV (ROI2) were similar but maximum load increased. At 12 weeks, the maximum load and also BV (ROI1, ROI2) were increased in the low-rigidity group.

Interpretation The low-rigidity nail manufactured from Ti-24Nb-4Zr-7.9Sn showed better external callus formation, seemed to reduce effects of stress shielding, and reduced bone resorption better than the stiffer nail. The low-rigidity nail was strong enough to maintain alignment of the fracture in the osteoporotic rat model without delayed union.     

The effect of levodopa or levodopa-carbidopa (sinemet) on fracture healing

OBJECTIVES: Levodopa (L-dopa) and L-dopa/carbidopa were evaluated to determine their effectiveness in the stimulation of bone healing of fractures at risk for nonunions. METHODS: Forty-two retired breeder female Sprague-Dawley rats were divided into 2 experimental groups and 1 control. Thirty-six rats were evaluated for results. The right femur of each rat was fractured and an intramedullary omega pin was inserted to create a 2 mm bone gap. The rats were administered either 0.2 g/kg/d of L-dopa, 0.2/0.02 g/kg/d L-dopa/carbidopa in their feed, or plain powdered chow (Sham control group). The rats were killed at 5 weeks postsurgery. The femurs were excised, radiographed, and mechanically tested. Bone healing was assessed. Bone stiffness, ultimate load, and energy to failure were determined under 3 point bending using an Instron materials testing system. RESULTS: The femurs of 30% of the Sham rats healed compared with 50% of the L-dopa/carbidopa and 84% of the L-dopa treated femurs. The healed L-dopa rat femurs had significantly greater ultimate load (P = 0.037) and energy to failure (P = 0.004) than the healed Sham rats. There were no significant differences between the L-dopa/carbidopa group and either the Sham or L-dopa group. CONCLUSIONS: These results confirm that L-dopa administration increases the healing in nonunion fractures. The combination of L-dopa/carbidopa did not significantly increase fracture healing.     

Development of an atrophic nonunion model and comparison to a closed healing fracture in rat femur.

Although most fractures heal, some fail to heal and become nonunions. Many animal models have been developed to study problems of fracture healing. The majority of nonunion models have involved segmental bone defects, but this may not adequately represent the biologic condition in which nonunions clinically develop. The objective of the present study is to develop a nonunion model that better simulates the clinical situation in which there is soft tissue damage including periosteal disruption and to compare this model to a standard closed fracture model utilizing identical fracture stabilization, providing a similar mechanical environment. A total of 96 three month old Long Evans rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three-point bending device. To create a nonunion, 48 of the rats received additional surgery to the fractured femur. The fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. Fracture healing was evaluated with serial radiographs every two weeks. Animals were maintained for intervals of two, four, six or eight weeks after surgery. Specimens from each time interval were subjected to biomechanical and histological evaluation. None of the cauterized fractures healed throughout the eight weeks experimental duration. The radiographical appearance of nonunion models was atrophic. This investigation showed pronounced differences between the experimental nonunions and standard closed fractures both histologically and biomechanically. In conclusion, we have developed a reproducible atrophic nonunion model in the rat femur that simulates the clinical condition in which there is periosteal disruption but no bone defect.     

Mechanical Properties of Fractured and Intact Rat Femora Evaluated by Bending, Torsional and Tensile Tests

Mechanical properties of healing fractures and growing, intact bones were studied in male rats aged 8 weeks at the beginning of the study period. A standardized, closed fracture was produced in the middle of the left femur. The fracture was not immobilized. At various intervals after the fracture, the healing fractured femora and the contralateral, intact femora were subjected to bending, torsional and tensile tests.

The fractured femora regained the strength and the ultimate deformation of the contralateral, intact femora after about 8 weeks when tested in bending, and after about 13 weeks when tested in torsion. In the first phases of fracture repair, the healing fractures could resist more torsional than bending load, whereas the opposite was found for solidly consolidated fractures and intact bones.

For intact bones, the ultimate bending and torsional moments increased with increase in age and weight of the animals, whereas the ultimate angular deformation remained constant. The ultimate bending and torsional stresses (bone material strength) increased to reach a plateau when the rats were about 14 weeks old. No significant differences were observed between the bending, torsional and tensile test methods. For the evaluation of fracture repair, each test has its particular application.     

Biomechanical analysis of supracondylar femoral fractures fixed with modern retrograde intramedullary nails

OBJECTIVES: Several new retrograde supracondylar intramedullary nails have been developed to specifically address fractures of the distal femur. The nails appear clinically effective, but there are few biomechanical data documenting the stability of the fixation or the mechanical stiffness of the different designs. The goal of this study was to assess the torsional and bending stiffness of four designs of intramedullary nails developed for this application. METHODS: Four nail designs were tested in torsion and bending to determine system stiffness: Ace supracondylar, Richards "five hole" and "multi-hole" supracondylar, and Biomet retrograde. The nails were inserted into cadaveric femurs in which a one-centimeter distraction osteotomy had been created seven centimeters proximal to the condyles. The constructs were then tested on an Instron biaxial testing system. RESULTS: There were no statistically significant differences in bending stiffness among the groups of nails (range 0.79 to 1.18 newtons/meter; p > 0.1). However, the Ace nails (1.10 newtonmeters/degree) did exhibit a statistically lower torsional stiffness compared with the other nails (2.20 to 2.21 newton-meters/ degree; p < 0. 1). No differences were noted as a function of the number of locking holes. CONCLUSIONS: The bending stiffness of four currently available designs of retrograde intramedullary nails does not appear to be dependent on design variations. The torsional stiffness did vary among the four designs, but this was not determined by the number of fixation holes provided. It appears that a well-placed retrograde supracondylar nail of modern design should have sufficient stiffness to support the femur and provide stability during fracture healing.     

Delayed Fracture Healing in Aged Senescence-Accelerated P6 Mice

ABSTRACT

Background: Osteoporosis is characterized by poor bone quality. However, it is still controversially discussed whether osteoporosis compromises fracture healing. Herein, we studied whether the course of healing of a femur fracture is affected by osteoporosis or age. Methods: Using the senescence-accelerated osteoporotic mouse, strain P6 (SAMP6), and a closed femur fracture model, we studied the process of fracture healing in 5- and 10-month-old animals, including biomechanical, histomorphometric, and protein biochemical analysis. Results: In five-month-old osteoporotic SAMP6 mice, bending stiffness, callus size, and callus tissue distribution as well as the concentrations of the bone formation marker osteocalcin and the bone resorption markers tartrate-resistant acid phosphatase form 5b (TRAP) and deoxypyridinoline (DPD) did not differ from that of non-osteoporotic, senescence-resistant, strain 1 (SAMR1) controls. In contrast, femur fractures in 10-month-old SAMP6 mice showed a significantly reduced bending stiffness and an increased callus size compared to fractures in age-matched SAMR1 controls. This indicates a delayed fracture healing in advanced age SAMP6 mice. The delay of fracture healing was associated with higher concentrations of TRAP and DPD. Significant differences in osteocalcin concentrations were not found between SAMP6 animals and SAMR1 controls. Conclusion: In conclusion, the present study indicates that fracture healing in osteoporotic SAMP6 mice is not affected in five-month-old animals, but delayed in animals with an age of 10 months. This is most probably due to the increased osteoclast activity in advanced age SAMP6 animals.     

卵巢切除对大鼠关节内骨折后软骨愈合的影响

目的探讨骨质疏松对大鼠关节内骨折后软骨愈合的影响。方法16只4.5月龄的雌性SD大鼠分为两组,实验组行双侧卵巢切除,对照组施行假手术。10周后,经手术制造右胫骨平台内髁劈裂骨折,克氏针交叉内固定。术后大鼠自由活动,6周后全部处死,标本行大体和组织学观察。结果所有标本骨折均愈合。实验组胫骨平台内侧关节软骨多不平整伴轻度塌陷,软骨裂隙依稀可辨,色泽稍暗;对照组内侧关节软骨多平整光滑,软骨裂隙消失。HE染色光镜观察发现,实验组关节软骨裂隙处可见较多纤维组织,透明样软骨呈岛状散在分布于关节表面;对照组多为透明样软骨,细胞排列较规则,但未见明显分层及潮线。结论卵巢切除导致大鼠骨质疏松,延缓了关节内骨折后软骨愈合的进程,且软骨愈合质量较差。     

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     

Effect of Stabilization on the Healing Process of Femur Fractures in Aged Mice

Background: The influence of mechanical stability on fracture healing has previously been studied in adult mice, but is poorly understood in aged animals. Therefore, we herein studied the effect of stabilization on the healing process of femur fractures in aged mice. Methods: Twenty-four 18-month-old CD-1 mice were stabilized after midshaft fracture of the femur with an intramedullary screw. In another 24 18-month-old mice, the femur fractures were left unstabilized. Bone healing was studied by radiological, biomechanical, histomorphometric, and protein expression analyses. Results: After 2 and 5 weeks of healing, the callus of nonstabilized fractures compared to stabilized fractures was significantly larger, containing a significantly smaller amount of osseous tissue and a higher amount of cartilaginous tissue. This was associated with a significantly lower biomechanical stiffness during the early phase of healing. However, during the late phase of fracture healing both nonstabilized and stabilized fractures showed a biomechanical stiffness of ～40%. Of interest, Western blot analyses of callus tissue demonstrated that the expression of proteins related to angiogenesis, bone formation and remodeling, i.e. VEGF, CYR61, BMP-2, BMP-4, Col-2, Col-10, RANKL, OPG, did not differ between nonstabilized and stabilized fractures. Conclusion: Nonstabilized fractures in aged mice show delayed healing and remodeling. This is not caused by an altered protein expression in the callus but rather by the excessive interfragmentary movements.     

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.     

Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats.

The impact of age and ovariectomy on the healing of femoral fractures was studied in three groups of female rats at 8, 32 and 50 weeks of age at fracture. In the two older groups, the rats had been subjected to ovariectomy or sham surgery at random at 26 weeks of age. At fracture, all rats received unilateral intramedullary pinning of one femur and a middiaphyseal fracture. Rigidity and breaking load of the femora were evaluated at varying times up to 24 weeks after fracture induction by three-point bending to failure. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. In the youngest group, 8-week-old female rats regained normal femoral rigidity and breaking load by 4 weeks after fracture. They exceeded normal contralateral values by 8 weeks after fracture. In the middle group, at 32 weeks of age, fractures were induced, and the femora were harvested at 6 and 12 weeks after fracture. At 6 weeks after fracture there was partial restoration of rigidity and breaking load. At 12 weeks after fracture, only the sham-operated rats had regained normal biomechanical values in their fractured femora, while the fractured femora of the ovariectomized rats remained significantly lower in both rigidity and breaking load. In contrast, for the oldest group of rats, 50 weeks old at fracture, neither sham-operated nor ovariectomized rats regained normal rigidity or breaking load in their fractured femora within the 24 weeks in which they were studied. In all fractured bones, there was a significant increase in BMD over the contralateral intact femora due to the increased bone tissue and bone mineral in the fracture callus. Ovariectomy significantly reduced the BMD of the intact femora and also reduced the gain in BMD by the fractured femora. In conclusion, age and ovariectomy significantly impair the process of fracture healing in female rats as judged by measurements of rigidity and breaking load in three-point bending and by accretion of mineral into the fracture callus.