Vascularised fibular graft in the management of femoral head osteonecrosis: twenty years later.

The management of osteonecrosis of the femoral head ranges from symptomatic therapy to total hip replacement. Conservative treatment is effective only in small, early-stage lesions. Free vascularised fibular grafting has provided more consistently successful results than any other joint-preserving method. It supports the collapsing subchondral plate by primary callus formation, reduces intra-osseous pressure, removes and replaces the necrotic segment, and adds viable cortical bone graft plus fresh cancellous graft, which has osseoinductive and osseoconductive potential. Factors predisposing to success are the aetiology, stage and size of the lesion. Furthermore, it is a hip-salvaging procedure in early pre-collapse stages, and a time-buying one when the femoral head has collapsed.

Synovial fluid metabolites in osteonecrosis.

OBJECTIVES: Osteonecrosis of the femoral head results from interruption of the vascular supply and eventual death of the cellular portion of bone. Effective methods of monitoring response to treatment are needed. Our aim was to evaluate synovial fluid metabolites, glucose and lactate, as biomarkers in a canine model of osteonecrosis. METHODS: Osteonecrosis was cryosurgically induced in the right femoral head while the left hip served as control (n = 31). Animals either underwent no further intervention (n = 10), vascular endothelial growth factor (VEGF) injections (n = 4), placement of a vascularized bone graft (n = 6), a combination of VEGF microinjection and vascularized graft placement (n = 5), or treatment with daily oral alendronate (n = 6). After 12 weeks, synovial fluid from each hip joint was obtained for glucose and lactate concentrations. RESULTS: Joints with surgically induced osteonecrosis demonstrated decreased synovial fluid concentrations of glucose (P < 0.05) and elevated concentrations of lactate (P < 0.05) relative to contralateral control hips. When animals were treated with VEGF, the vascularized graft placement, or vascularized graft and VEGF, there were no differences in the synovial fluid concentrations of these metabolites between cryoablated and control hips. In contrast, alendronate did not normalize the concentration of these synovial fluid metabolites in the cryoablated hips. CONCLUSIONS: Osteonecrosis of the femoral head is associated with alterations in synovial fluid glucose and lactate, reflecting anaerobic metabolism. These metabolites may serve as useful tools for monitoring response to revascularization therapies.

Gene and protein expressions of nitric oxide synthases in ischemia-reperfused peripheral nerve of the rat.

This study examined mRNA and protein expressions of neuronal (nNOS), inducible (iNOS), and endothelial nitric oxide synthases (eNOS) in peripheral nerve after ischemia-reperfusion (I/R). Sixty-six rats were divided into the ischemia only and I/R groups. One sciatic nerve of each animal was used as the experimental side and the opposite untreated nerve as the control. mRNA levels in the nerve were quantitatively measured by competitive PCR, and protein was determined by Western blotting and immunohistochemical staining. The results showed that, after ischemia (2 h), both nNOS and eNOS protein expressions decreased. After I/R (2 h of ischemia followed by 3 h of reperfusion), expression of both nNOS and eNOS mRNA and protein decreased further. In contrast, iNOS mRNA significantly increased after ischemia and was further upregulated (14-fold) after I/R, while iNOS protein was not detected. The results reveal the dynamic expression of individual NOS isoforms during the course of I/R injury. An understanding of this modulation on a cellular and molecular level may lead to understanding the mechanisms of I/R injury and to methods of ameliorating peripheral nerve injury.

Comparison of continuous and interrupted suture techniques in microvascular anastomosis.

We evaluated the efficacy of the continuous suture technique (CST) in arteries and veins with varying external diameters (ED). In study 1 a direct end-to-end anastomosis was performed in 5 groups of animals (n = 15 in each group): group 1, rabbit carotid artery (ED, 1.8-2.0 mm); group 2, rabbit femoral artery (ED, 1.4-1.6 mm); group 3, rat femoral artery (ED, 0.7-0.9 mm); group 4, rabbit femoral vein (ED, 2.0-2.2 mm); and group 5, rat femoral vein (ED, 1.0-1.2 mm). In study 2 a graft from the femoral vein was interposed into the carotid artery, with a ratio of the diameter of graft to artery of 1.3:1 in the rats (group 6, n = 12) and 1:1 in the rabbits (group 7, n = 12). In each animal the vessel on one side was repaired using CST and the opposite vessel using the interrupted suture technique. Vessel samples were harvested 1, 2, and 4 weeks after anastomosis. The CST significantly reduced anastomosis time by up to 47% in arteries and 41% in veins. Bleeding time and blood loss were also significantly reduced with CST. Similar results were found in study 2. The total thrombosis rate was 8%, but no significant patency difference was noted between the CST and the interrupted suture technique in any vessel category. We conclude that the CST is a reliable and time-saving procedure in microvascular anastomosis of arteries with diameters greater than 0.7 mm and of veins with diameters greater than 1.0 mm.

Treatment of osteonecrosis in the hip of pediatric patients by free vascularized fibular graft.

The purpose of the current study was to review the demographics and etiologies of symptomatic femoral head osteonecrosis in the pediatric and adolescent population and to assess the results of treatment using free vascularized fibular grafting. A group of patients with femoral head osteonecrosis who were treated with free vascularized fibular grafting was reviewed. Patients who were studied were 18 years of age or younger at the time of surgery. Records were examined for demographic data, etiology of osteonecrosis, stage of the disease at time of surgery, and results of treatment including preoperative and postoperative Harris hip scores. Eighty-two pediatric and adolescent patients with osteonecrosis of the femoral head underwent 90 free vascularized fibular grafting procedures. Fifty patients (54 hips) who have been followed up at least 2 or more years (average, 4.3 years) constituted the study group. At the last followup, total hip arthroplasty was performed in seven hips (seven patients) and hip fusion was performed in one hip (one patient). The average Harris hip scores in patients who did not undergo total hip arthroplasty improved from a preoperative average of 55.3 points to 90.2 points at the latest followup. Treatment of patients with osteonecrosis with free vascularized fibular grafting resulted in a lower rate of conversion to total hip arthroplasty or fusion (16%) in pediatric and adolescent patients when compared with conversion to total hip arthroplasty in adults (25%). The quality of life as evidenced by the increased Harris hip scores was improved significantly in this group of pediatric and adolescent patients.

Hemorrhage and thrombus formation in early experimental osteonecrosis.

The aim of the current study was to test the hypothesis that the induction of an underlying immunologic condition in rabbits may enhance the development of steroid-induced osteonecrosis. Thirty-five adult rabbits were divided into four groups. Group I: 10 rabbits were immunized at 15-day intervals for 2 months by murine antibodies to deoxyribonucleic acid autoantibodies. Four weeks after the end of the immunization, the animals received injections of methylprednisolone for 7 days and then prednisolone per os for 8 months. Group II: 10 animals only received immunizations according to the protocol used in Group I. Group III: 10 animals only were treated with corticosteroids according to the protocol used in Group I. Group IV: five animals were used as controls. Various changes were observed in the proximal metaphysis and diaphysis of the femur in eight of 10 animals in Group I (80%) and in five of 10 animals in Group II (50%) when compared with the animals in Group III and Group IV. The most common feature was evidence of new and old hemorrhage through the sinusoids, exudative reaction and thrombus formation in veins and small arteries. Focal necrotic areas of bone marrow showed an accumulation of cell debris, residue of hemorrhage, and disappearance of marrow elements. These findings suggest that (1) corticosteroids may potentiate the effects of a preexisting condition to increase the risk of osteonecrosis; (2) immunologic reaction may be an important factor in the pathogenesis of necrotic lesions; and (3) repeated intramedullary hemorrhage and thrombus formation may represent early major pathologic findings in bone necrosis.

Blockade of L-selectin attenuates reperfusion injury in a rat model.

Ischemia/reperfusion (I/R) injury appears to be a significant neutrophil-dependent component and may be ameliorated by blocking leukocyte-endothelial adhesion. Using a rat extensor digitorum longus (EDL) muscle model, the present study tested the hypothesis that in vivo administration of the function-blocking monoclonal antibody (mAb) LAM1-116 which recognizes L-selectin, a cell-surface adhesion receptor, could decrease I/R injury. In 46 rats, one EDL served as a normal control and the opposite EDL underwent 3 hr of ischemia followed by 3 hr of reperfusion after pretreatment with LAM1-116 mAb, control IgG, or saline. Myeloperoxidase (MPO) activity showed only a two-fold increase from normal in LAM1-116-treated I/R EDL while a 27-fold increase occurred in the IgG2a and saline groups, with a statistically significant (p < 0.001) difference. A significantly (p < 0.05) lower wet weight ratio, improved fatigue contractile force, and less neutrophil infiltration were found in LAM1-116-treated EDL, when compared to those in control IgG- or saline-treated EDL. The results indicate that blockade of L-selectin by LAM1-116 mAb can effectively reduce neutrophil infiltration in reperfused skeletal muscle, thereby decreasing tissue edema and improving muscle fatigue contractile force. These findings may be important in understanding I/R injury.

End-to-side nerve repair. A review.

In recent years, there has been a resurgence of end-to-side peripheral nerve repair. This technique offers a management of a peripheral nerve defect in the absence of a suitable proximal stump. Although numerous animal laboratory investigations demonstrate motor and sensory functional recovery without deleterious effects to the donor nerve, clinical outcomes are yet to be determined.

Interleukin-1 beta promotes functional recovery of crushed peripheral nerve.

This study was conducted to elucidate the role of the cytokine interleukin-1 beta on peripheral nerve recovery following crush injuries of two different magnitudes. Eighty-eight female rats were divided into four groups. A 5-mm segment of the right sciatic nerve was subjected to a 100-g crush load for 2 hours in the rats in Groups A1 and B1 or to a 15,000-g crush load for 10 minutes in the rats in Groups A2 and B2. The rats in Groups A1 and A2 received 10 microg/100 g body weight human recombinant interleukin-1 beta intraperitoneally 48, 24, and 1 hours before the nerve injury. The rats in Groups B1 and B2 were treated with an equal volume of normal saline solution with identical schedule guidelines. Walking-track tests (sciatic functional index) performed at intervals until 56 days after the crush and measurements of the contractile force of the extensor digitorum longus muscle made until 28 days were used to evaluate functional recovery of the nerve. During the second week after injury, the rats treated with interleukin-1 beta (A1) had an earlier recovery on the walking track than did those treated with saline solution (B1); this difference reached significance (p < 0.05) at day 11. Although Group A2 demonstrated a trend toward earlier recovery compared with Group B2, there was no significant difference between the two groups. After low or high-load crush injury, tetanic contractile forces were greater in the rats treated with human recombinant interleukin-1 beta than in those treated with saline solution. The results suggest that treatment with human recombinant interleukin-1 beta before crush injury can promote function in the peripheral nerve after the injury. However, the mechanisms that underlie the observed beneficial effects are not completely understood and only speculations can be made.

Osteonecrosis of the femoral head associated with pregnancy. A preliminary report.

BACKGROUND: Osteonecrosis is usually associated with trauma, use of corticosteroids, or alcohol abuse. We investigated the rare association of osteonecrosis of the femoral head and pregnancy, and we defined differences between the disorder in pregnant women and that in women of childbearing age who were not pregnant. The results of treatment with a free vascularized fibular graft were evaluated in terms of relief of pain and improvement of the Harris hip score after a minimum of two years of follow-up. METHODS: Thirteen women (seventeen hips) had the onset of pain in the hip during pregnancy or within the first four weeks after delivery, and the pain persisted until a diagnosis of osteonecrosis of the femoral head was made on the basis of magnetic resonance imaging. No patient had any other risk factor for this disease. Information was obtained by means of clinical assessment, a review of the records and radiographs, and a telephone survey. Eleven women (fifteen hips) were managed with a free vascularized fibular graft, and nine of them (eleven hips) were evaluated, with regard to relief of pain and the Harris hip score, at a minimum of two years postoperatively. RESULTS: The average age when the pain began was 31.5 years (range, twenty-five to forty-one years). Eleven of the thirteen women were primigravid, and the patients typically first had the pain late in the second trimester or in the third trimester of pregnancy. The women tended to have a small body frame and a relatively large weight gain during the pregnancy. Eight of the thirteen patients had swelling and varicosity of the lower extremities. The diagnosis was delayed an average of 10.3 months, with a range of three to thirty months. A common misdiagnosis was transient osteoporosis of the hip during pregnancy. A correct diagnosis was established for all hips on the basis of the finding of a double-density signal on magnetic resonance imaging or evidence of progression of the disease on plain radiographs. According the system of Marcus et al., the stage at the time of diagnosis ranged from II to V. All women had involvement of the left hip, and four had bilateral involvement. Of the eleven women (fifteen hips) who were managed with a free vascularized fibular graft, nine noted marked or complete relief of the preoperative pain. Two hips in a patient who had progressive pain were treated with a total hip arthroplasty. Two hips (one patient) were lost to follow-up. The nine patients (eleven hips) who were available for follow-up at a minimum of two years had an average improvement in the Harris hip score of 24 points. CONCLUSIONS: Occasionally, pain in the hip that begins during pregnancy is caused by osteonecrosis of the femoral head. A high index of suspicion and use of magnetic resonance imaging may lead to an earlier diagnosis and a better prognosis in this population of women. In this study, treatment with a free vascularized fibular graft was a useful option with which to obviate or postpone the need for total hip arthroplasty.

Influences of inflation rate and duration on vasodilatory effect by intermittent pneumatic compression in distant skeletal muscle.

Previous study has demonstrated that application of intermittent pneumatic compression on legs can cause vasodilation in distant skeletal muscle at the microcirculation level. This study evaluated the influence of inflation rate and peak-pressure duration on the vasodilatory effects of intermittent pneumatic compression. The cremaster muscles of 50 male rats were exposed and divided into five groups of 10 each. A specially designed intermittent pneumatic-compression device was applied in a medial-lateral fashion to both legs of all rats for 60 minutes, with an inflation rate and peak-pressure duration of 0.5 and 5 seconds, respectively, in group A, 5 and 0 seconds in group B, 5 and 5 seconds in group C, 10 and 0 seconds in group D, and 10 and 5 seconds in group E. Diameters of arterial segments were measured in vessels of three size categories (10-20, 21-40, and 41-70 microm) for 120 minutes. The results showed that the greatest increase in diameter was produced by intermittent pneumatic compression with the shortest inflation rate (0.5 seconds). A moderate increase resulted from compression with an inflation rate of 5 seconds, and no effective vasodilation occurred during compression with the longest inflation rate (10 seconds). When the groups with different inflation rates but the same peak-pressure duration were compared, there was a significant difference between any two groups among groups A, C, and E and between groups B and D. When the groups with different peak-pressure durations but the same inflation rate were compared, compression with a peak-pressure duration of 5 seconds caused a generally similar degree of diameter change as did compression without inflation at peak pressure. The findings suggest that inflation rate plays an important role in the modulation of distant microcirculation induced by intermittent pneumatic compression whereas peak-pressure duration does not significantly influence the vasodilatory effects of the compression. This may be due to the fact that rapid inflation produces a significant increase in shear stress on the vascular wall, which stimulates vascular endothelium to release nitric oxide, causing systemic vasodilation.

Motor functional and morphological findings following end-to-side neurorrhaphy in the rat model.

Nerve repair cannot always be achieved by the conventional end-to-end technique. This study evaluated the functional recovery of nerves repaired with end-to-side neurorrhaphy in a rat model. The right peroneal nerves of 80 female rats were transected and divided into four groups. In group A, the nerve ends were separated and remained unrepaired; in group B, the distal peroneal ends were directly sutured to the epineurium of the tibial nerves in end-to-side fashion; in group C, the distal ends were sutured through an epineurial window at the repair site in end-to-side fashion; and in group D, the nerve ends were reconnected by the traditional end-to-end technique. Evaluation included gait analysis by calculation of a peroneal functional index, measurement of contractile function of the extensor digitorum longus muscle, wet weight of the extensor digitorum longus, and histological examination. The findings of this study suggested the following: (a) end-to-side neurorrhaphy allows effective motor functional recovery, demonstrated by earlier improvement of the peroneal functional index, stronger muscle contractile function, greater muscle weight, and higher density of regenerated axons compared with unrepaired nerves; (b) removal of the epineurium of the donor nerve at the nerve coaptation site increases the effectiveness of end-to-side neurorrhaphy, but the epineurium appears to be a partial barrier to axonal regeneration; (c) removal of the epineurium does not affect the structure and function of the donor nerve; and (d) end-to-end repair achieved the best functional recovery among the four groups; therefore, end-to-side repair should be considered as a potential alternative only when no proximal nerve is available.

Intermittent pneumatic compression of legs increases microcirculation in distant skeletal muscle.

Intermittent pneumatic compression has been established as a method of clinically preventing deep vein thrombosis, but the mechanism has not been documented. This study observed the effects of intermittent pneumatic compression of legs on the microcirculation of distant skeletal muscle. The cremaster muscles of 80 male rats were exposed, a specially designed intermittent pneumatic-compression device was applied to both legs for 60 minutes, and the microcirculation of the muscles was assessed by measurement of the vessel diameter in three categories (10-20, 21-40, and 41-70 microm) for 120 minutes. The results showed significant vasodilation in arterial and venous vessels during the application of intermittent pneumatic compression, which disappeared after termination of the compression. The vasodilation reached a maximum 30 minutes after initiation of the compression and could be completely blocked by an inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (10 micromol/min). A 120-minute infusion of NG-monomethyl-L-arginine, beginning coincident with 60 minutes of intermittent pneumatic compression, resulted in a significant decrease in arterial diameter that remained at almost the same level after termination of the compression. The magnitude of the decrease in diameter in the group treated with intermittent pneumatic compression and NG-monomethyl-L-arginine was comparable with that in the group treated with NG-monomethyl-L-arginine alone. The results imply that the production of nitric oxide is involved in the positive influence of intermittent pneumatic compression on circulation. It is postulated that the rapid increase in venous velocity induced by intermittent pneumatic compression produces strong shear stress on the vascular endothelium, which stimulates an increased release of nitric oxide and thereby causes systemic vasodilation.

Effect of a NOS inhibitor, L-NMMA, on the contractile function of reperfused skeletal muscle.

The authors investigated the effect of NG-monomethyl-L-arginine acetate (L-NMMA), a nitric oxide synthase (NOS) inhibitor, on the contractile function of skeletal muscle following ischemia/reperfusion (I/R) injury. The extensor digitorum longus (EDL) muscles of 50 rats were divided into seven groups. Contractile function in non-ischemic EDL did not change statistically significantly with L-NMMA infusion. I/R (1.5 hr I and 3 hr R) significantly decreased EDL contractile function, with an average maximal twitch force of 56 percent of the contralateral normal muscle force and isometric tetanic contractile forces between 47 and 84 percent at four different stimulation frequencies. Following L-NMMA administration at three different dosages, contractile function of I/R muscle decreased in a dose-dependent manner. The highest dosage of L-NMMA (10 micromol/min) reduced the average maximal twitch force to 15 percent and the isometric tetanic contractile forces to between 10 to 23 percent. Histologic evaluation revealed increased edema, neutrophil infiltration, and muscle-fiber necrosis in L-NMMA-infused EDL, compared to the controls. 1) Skeletal muscle contractile function was dose-dependently decreased with the administration of L-NMMA during I/R. 2) The concentrations of L-NMMA used in this study did not influence the function of non-ischemic EDL. These findings suggest that reduction of NO production during I/R is damaging to skeletal muscle function and would impair successful functional outcomes in microsurgical replantation.

Recombinant human glial growth factor 2 (rhGGF2) improves functional recovery of crushed peripheral nerve (a double-blind study).

This in vivo double-blind study evaluated the effect of recombinant human glial growth factor 2 (rhGGF2), a Schwann cell mitogen, on the recovery of motor function of rat sciatic nerve following crush injury. Seventy three rats were divided into three groups. Group I (n=5), sham operated; Groups II (n=34) and III (n=34) received a 100 g crush load for 2 h over a 5 mm segment of the sciatic nerve. Group III was treated with 1 mg/kg rhGGF2, via subcutaneous injection one day before nerve crush and daily for the following four days. Group II received an equivalent volume of saline as a control. Motor functional recovery was assessed by calculating the sciatic functional index (SFI) and the recovery rate of tetanic contractile force of the extensor digitorum longus (EDL) muscle. Recovery of nerve function was evident at day 11 after crush in the rhGGF2-treated animals, whereas the nerves in controls were still paralyzed. The rhGGF2-treated animals showed a significant improvement of the SFI between days 11-21 postoperatively when compared to controls. The isometric tetanic contractile force was stronger in the rhGGF2-treated group than in controls, with a significant difference at 40 to 70 Hz stimulus frequencies on day 4. Correlation analysis showed that tetanic contractile force had a linear correlation with the SFI. Histologic assessment indicated that the rhGGF2-treated animals showed less severe degeneration and earlier robust remyelination of axons than controls. The results suggest that treatment with rhGGF2 is effective in promoting nerve regeneration as seen in measurements of functional recovery and qualitative assessment of nerve morphology. The mechanism of GGF's protective effect may be related to its direct action on Schwann cells, stimulating their mitosis as well as inducing neurotrophic factors essential to neuronal maintenance and repair.

S-nitroso-N-acetylcysteine protects skeletal muscle against reperfusion injury.

The effects of a nitric oxide (NO) donor on microcirculation and contractile function of reperfused skeletal muscle were studied. Rat cremaster muscles underwent 5 hours of ischemia and 90 minutes of reperfusion and were divided into two groups systemically infused with S-nitroso-N-acetylcysteine (SNAC, 100 nmol/min) and phosphate-buffered saline (PBS), respectively. The results showed that the vessels in the SNAC group had more rapid and complete recovery than that in controls. A significant difference was found from 10 to 40 minutes and at 90 minutes in 10-20-microm arterioles, from 10 to 90 minutes in 20-40-microm arterioles, and at 10 and 90 minutes in 40-70-microm arteries. When compared to controls, SNAC-treated muscles showed larger fluorescein filling areas at 15, 30, 60, and 90 minutes and greater isometric tetanic contractile forces in response to stimulation frequencies of 40, 70, 100, and 120 Hz. The data indicate that supplementation of exogenous NO could effectively improve microcirculation and contractile function of skeletal muscle during early reperfusion.

Survival analysis of hips treated with core decompression or vascularized fibular grafting because of avascular necrosis.

Avascular necrosis of the femoral head is a multifaceted process that leads to articular incongruity and subsequent osteoarthrosis of the joint. Clinicians concur that primary treatment should focus on preservation of the natural surface of the joint; however, there has not been a consensus on how best to accomplish this. While a number of therapeutic interventions have been reported, the efficacy has varied markedly and there have been few statistical comparisons. The purpose of the current study was to use statistical analysis to compare the results of two widely used procedures, vascularized fibular grafting (614 hips; 480 patients) and core decompression (ninety-eight hips; seventy-two patients), for the treatment of avascular necrosis. The patients were stratified according to age and the stage of disease, and a survival analysis was performed with total hip arthroplasty as the end point for failure. None of the eleven hips that had Ficat stage-I disease needed a total joint replacement after being treated with either regimen. Analysis of the hips that had stage-II disease revealed rates of survival, at fifty months, of 65 per cent (twenty-eight of forty-three hips) after core decompression and 89 per cent (ninety-nine of 111 hips) after vascularized fibular grafting. For the hips that had Ficat stage-III disease, the rates of survival at fifty months were 21 per cent (ten of forty-seven hips) after core decompression and 81 per cent (405 of 500 hips) after vascularized fibular grafting. Among the hips that had Ficat stage-II or III disease, the rate of eventual total joint arthroplasty after vascularized fibular grafting was significantly lower than that after core decompression (p < 0.0001). The results indicate that the increased morbidity associated with vascularized fibular grafting is justified by the associated delay in or prevention of articular collapse in hips that have stage-II or III disease.

Revascularization of the femoral head in osteonecrosis.

Osteonecrosis of the femoral head accounts for as many as 18% of total hip arthroplasties performed in western countries. The young age of affected patients and the potentially poor outcome have sparked an interest in alternative treatment modalities. Extracapsular placement of a vascularized fibular graft in the subchondral region of the femoral head has shown great promise as a treatment option. The authors have used this procedure in the treatment of 646 symptomatic hips, of all grades of osteonecrosis, with a follow-up of 1 to 17 years. The resultant 10-year survival rate of greater than 80% suggests that this procedure may be preferable to total hip arthroplasty for the young patient with osteonecrosis of the femoral head.