Pediatric solid organ transplantation and osteoporosis: a descriptive study on bone histomorphometric findings.

BACKGROUND: Organ transplantation may lead to secondary osteoporosis in children. This study characterized bone histomorphometric findings in pediatric solid organ transplant recipients who were assessed for suspected secondary osteoporosis. METHODS: Iliac crest biopsies were obtained from 19 children (7.6-18.8 years, 11 male) who had undergone kidney (n = 6), liver (n = 9), or heart (n = 4) transplantation a median 4.6 years (range 0.6-16.3 years) earlier. All patients had received oral glucocorticoids at the time of the biopsy. RESULTS: Of the 19 patients, 21 % had sustained peripheral fractures and 58 % vertebral compression fractures. Nine children (47 %) had a lumbar spine BMD Z-score below -2.0. Histomorphometric analyses showed low trabecular bone volume (< -1.0 SD) in 6 children (32 %) and decreased trabecular thickness in 14 children (74 %). Seven children (37 %) had high bone turnover at biopsy, and low turnover was found in 6 children (32 %), 1 of whom had adynamic bone disease. CONCLUSIONS: There was a great heterogeneity in the histological findings in different transplant groups, and the results were unpredictable using non-invasive methods. The observed changes in bone quality (i.e. abnormal turnover rate, thin trabeculae) rather than the actual loss of trabecular bone, might explain the increased fracture risk in pediatric solid organ transplant recipients.

Tissue restoration after implantation of polyglycolide, polydioxanone, polylevolactide, and metallic pins in cortical bone: an experimental study in rabbits.

We performed qualitative and histoquantitative investigations of tissue restoration after implanting polyglycolide (PGA), polydioxanone (PDS), polylevolactide (PLLA), and stainless steel pins in the intramedullary canal of rabbit femurs. The effect of bioabsorbable devices on healing of a cortical bone defect was also assessed. The cortical bone defect was created in the right femur of 80 rabbits. Bioabsorbable and metallic pins in 60 and two metallic pins alone were implanted in 20 intramedullary canals; 80 left femurs served as intact controls. Follow-up times were 3, 6, 12, 24, and 52 weeks. At all time points, collagenous connective tissue, including bone trabeculae, surrounded the implant at the tissue-implant interface, replacing hematopoiesis and fat of the intramedullary canal. The groups did not differ in the area and trabecular bone area fraction of the resulting callus. Residual fragments of PGA and PDS were observed at 24 weeks, and complete degradation occurred within 52 weeks. PGA, PDS, PLLA, and metallic implants induced a bony and fibrous walling-off response in the intramedullary cavity. No inflammation was observed. Complete tissue restoration did not occur within the follow-up, even after complete degradation of PGA and PDS, which had shorter degradation times than PLLA. The cortical bone healing effect was not different between bioabsorbable pins and metallic wires. Thus, these polymers had no specific osteostimulatory or osteoinhibitory properties compared to stainless steel. Within the follow-up period, there were no significant differences in biocompatibility between the implants and no adverse inflammatory foreign-body reactions.

One screening magnetic resonance imaging sequence in evaluation of chondral and meniscal lesions of the knee - a pilot study.

This prospective study aimed to evaluate if chondral and meniscal lesions in symptomatic knees of osteoarthritis patients can be reliably identified using only one sagittal dual-echo MRI (Magnetic Resonance Imaging) sequence. MRI was performed on 13 patients after knee arthroscopy due to knee pain and clinically suspected osteoarthritis using a 1.5-Tesla scanner with knee coil and a sagittal dual-echo turbo spin-echo PD (Proton Density)- and T2-weighted sequence. The MRI and arthroscopic findings were then compared. Of 65 articular surfaces, 47 were damaged. For articular cartilage lesions, the overall sensitivity of MRI was 46.8%, specificity 72.2%, and diagnostic accuracy 53.9%, and for meniscal ruptures 81.2%, 66.7%, and 73.1%, respectively. The present study showed that the reliability of screening MRI of knees using only one sagittal dual-echo sequence does not suffice for diagnosis of chondral or meniscal lesions, and should therefore not replace routine knee MRI or diagnostic arthroscopy.

Therapy insight: orthopedic complications after solid organ transplantation in childhood.

Several factors, such as immobilization, metabolic bone disease and immunosuppressive drugs, can compromise the quality of bone in children who have undergone solid organ transplantation. In contrast to adults, decreased bone mineral density has been reported in only a small proportion of pediatric transplant patients, and the relationship between low bone mineral density and fracture risk has not been established in children. Nevertheless, fractures, scoliosis, and joint and spinal degeneration are common in patients who received solid organ grafts as children. Avascular bone necrosis occurs infrequently in this patient population. Future studies should evaluate the effects of the underlying disease, transplantation and immunosuppression on the metabolism of bone and cartilage. On the basis of our own clinical experience and literature review, the growing spine of children who have received transplants should be continuously evaluated, and follow-up of bone mineral density is indicated. By contrast, routine MRI of the joints seems unnecessary.

Bilateral femoral fatigue fracture: an unusual fracture in a military recruit.

We present a case report of a military recruit who had bilateral fatigue fractures of the distal femur. Possible predisposing factors and the long-term outcome of these unusual stress fractures also are presented. A 19-year-old recruit experienced knee pain 2 weeks after starting his military service. Bilateral nondisplaced transverse fatigue fractures were detected radiographically in the supracondylar region on the right side and in the distal 1/3 of the femoral shaft on the left side. The fractures were treated with plaster casts for 5 weeks and healed properly. Osteopenia was seen in further examinations. At followup after 31 months followup the patient had fully resumed his previous athletic activity level and was symptom-free. Osteopenia still could be detected at the final examination. Nonoperative treatment with careful followup resulted in a favorable outcome in the nondisplaced bilateral distal fatigue femoral fractures in this patient.

Spine after solid organ transplantation in childhood: a clinical, radiographic, and magnetic resonance imaging analysis of 40 patients.

STUDY DESIGN: A cross-sectional study of the spine in 40 young adults after solid organ transplantation in childhood. OBJECTIVE: To evaluate the impact of organ transplantation and long-term immunosuppressive treatment on growing spine using magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: A review of the current literature reveals no systematic evaluation of the spine after transplantation in childhood. METHODS: A total of 40 adult patients (mean age 22.1 years, range, 16.0-27.0), who received either kidney, liver, or heart transplant as children, were evaluated. Mean follow-up after transplantation was 11.2 years (range 3.0-18.0). All patients filled in a questionnaire, underwent an interview and physical examination, as well as had MRI of the spine. Standing spinal radiographs were taken from patients with a rib hump > or = 6 degrees. RESULTS: There were 8 (20%) patients who had a history of vertebral fracture. Eleven (28%) patients reported frequent back pain at rest. There were 15 (38%) patients who had scoliosis > 10 degrees (range 10 degrees -69 degrees ). On MRI, narrowed disc spaces were noted in 32 (80%) patients, and irregular endplates were noted in 24 (60%). There were 14 (35%) patients who had at least 1 compressed or wedged vertebra (> 20%). Patients treated for acute rejection had wedged vertebrae, speckled or black disc spaces, and irregular endplates more often than patients without rejections. Males had wedged vertebrae more often than females (P = 0.0067). CONCLUSIONS: Back pain, scoliosis, wedged vertebrae, and narrowed, degenerated disc spaces are common after solid organ transplantation in childhood.

Avascular bone necrosis of the hip joint after solid organ transplantation in childhood: a clinical and MRI analysis.

BACKGROUND: Aseptic osteonecrosis is a well-known complication after solid organ transplantation in adults. The occurrence of osteonecrosis in growing age has been studied after kidney transplantation, but no systematic evaluation of the joints has been reported after heart or liver transplantation in childhood. METHODS: A total of 196 children--93% of patients surviving kidney, liver and heart transplantation in Finland--participated in a cross-sectional survey. All children underwent a detailed clinical examination and filled out a questionnaire on musculoskeletal symptoms. Radiographs were taken in case of joint pain or abnormal clinical findings. In addition, magnetic resonance imaging (MRI) from the hips was taken on a random basis from 34 adult patients transplanted as a child. The mean follow-up time of all patients after transplantation was 9.2 years (range, 2.4 to 20.5 years). RESULTS: Twenty-eight (14%) patients reported prolonged joint or limb pain without previous trauma. Specific etiology for the limb pain was not found in 10 (5.1%) patients. Osteonecrosis seen in radiographs or MRI was noted in seven (3.6%) patients, of which three had received kidney, three liver, and one heart graft. Femoral head was affected in five patients, as well as talus bilaterally in one patient and lateral femoral condyle in one patient. All patients were older than 12 years at the time of diagnosis of the osteonecrosis. MRI of the hips of 34 randomly selected patients showed only one asymptomatic necrosis of the femoral head. CONCLUSIONS: Symptomatic osteonecrosis of the hip is uncommon after solid organ transplantation in childhood using the current immunosuppressive medications.

Tissue response to polyglycolide, polydioxanone, polylevolactide, and metallic pins in cancellous bone: An experimental study on rabbits.

The purpose of this study was to investigate, qualitatively and histoquantitatively, the tissue response of rabbit femur cancellous bone to polyglycolide (PGA), polydioxanone (PDS), polylevolactide (PLLA), and stainless steel pins under identical conditions. Eighty knees in 50 rabbits were operated on by inserting bioabsorbable pins (PGA, PDS, or PLLA) together with metallic Kirschner wire in 60, and two metallic Kirschner wires alone in 20 knees, while 20 knees served as intact controls. Follow-up times were 3, 6, 12, 24, and 52 weeks. Cancellous bone tissue response to implants was studied using histological, histomorphometrical, microradiographical, and oxytetracycline fluorescence methods. Residual fragments of PGA and PDS were seen at 24 weeks. Complete degradation of these polymers had taken place before 52 weeks. No signs of degradation of the PLLA pins were observed within the entire follow-up period. The osteoid formation surfaces at tissue implant-interface were statistically larger in all test groups as compared to intact controls. The number of macrophages at tissue implant-interfaces increased in all bioabsorbable implant specimens until 6 weeks, and with PGA until 12 weeks. No differences in the osseous response emerged when comparing groups of bioabsorbable implants with each other or with stainless steel group. Bioabsorbable pins and metallic Kirschner wires evoked an osteoconductive response in the cancellous bone surrounding implant, but the response intensity between implants displayed no differences. This suggests a simple, nonspecific walling-off new-bone front type of response. Consequently, the polymers possessed no specific osteostimulatory or osteoinhibitory properties. Within the follow-up, no significant differences in biocompatibility between the implants appeared, and no frank inflammatory foreign-body reactions occurred. The small-volume pins obviously did not exceed the local tissue tolerance and clearing capacity of the bone.

Incidence and predictors of fractures in children after solid organ transplantation: a 5-year prospective, population-based study.

UNLABELLED: In this population-based prospective follow-up study, children undergoing solid organ transplantation had a highly elevated risk for fractures: The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p < 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p < 0.001) in the study group compared with the control population. Thus, screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied. INTRODUCTION: The incidence and predictors of fractures after solid organ transplantation are not well documented in the pediatric age group. MATERIALS AND METHODS: A total of 196 children, which is 93% of patients surviving kidney, liver, and heart transplantation in our country, participated in a retrospective chart review at enrollment followed by a 5-year prospective follow-up study between January 1999 and December 2004. Hospital and medical records were reviewed. All children underwent clinical examinations and answered questionnaires concerning fracture history at the beginning and at the end of the prospective follow-up. Radiographs of the thoracic and lumbar spine were obtained. The fracture incidence was compared with data obtained from public health registries. RESULTS: Seventy-five (38%) of the transplant patients suffered from a total of 166 fractures after organ transplantation. The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p < 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p < 0.001) in the study group compared with the control population. The age- and sex-adjusted hazard ratios (95% CI) were 61.3 (40.7-92.4) for vertebral, 17.9 (8.96-35.8) for symptomatic vertebral, 0.99 (0.65-1.50) for nonvertebral, and 2.90 (2.25-3.73) for all fractures in the patients compared with the control population. In a multivariate analysis, older age (hazard ratio [95% CI]; 2.02 [1.07-3.83]), male sex (2.15 [1.22-3.81]), liver transplantation (1.78 [1.01-3.14]), and fractures before transplantation (2.02 [0.92-4.47]) were the most significant independent risk factors. CONCLUSIONS: Children undergoing solid organ transplantation have a highly elevated risk for fractures. Screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied.

Displaced fatigue fractures of the femoral shaft.

For this study, all displaced fatigue fractures of the femoral shaft treated during a 20-year period at a national military hospital were analyzed. Ten previously healthy male recruits sustained displaced femoral shaft fatigue fractures, the incidence being 1.5 per 100,000 person-years in military service. The median age of the patients was 19 years (range, 18-20 years). None had any previous fatigue fractures. The median body mass index was normal. Before the fracture displacement, nine recruits experienced thigh or knee pain for 1 to 6 weeks. Six of the 10 fractures were located in the distal third of the diaphysis. Only one fracture occurred in the proximal third. Six fractures showed a noncomminuted, oblique, or oblique-transverse configuration. Five fractures were treated using an intramedullary nail, four fractures with a dynamic compression plate, and one with a dynamic condylar screw-plate. The bone at the site of fracture proved to be abnormally brittle. In six patients this resulted in additional comminution intraoperatively. Two reoperations were necessary to exchange a nail and a screw because of technical faults. The median time to solid bony union was 3.5 months (range, 3-5 months). The recruits returned to light duty military service 6 weeks postoperatively, on the average. Two were exempted from military service for 2 years. Displacement is a rare, highly undesirable consequence of fatigue osteopathy of the femoral shaft among young recruits during basic military training. Preventive methods should focus on early, effective detection of developing fatigue fractures to avoid a displaced fracture, with subsequent prolonged morbidity and possible complications. Gentle handling of the bone during the fracture fixation procedure is imperative because of the extraordinary brittleness of the fracture fragments.

The treatment of nonunions following intramedullary nailing of femoral shaft fractures.

OBJECTIVE: To assess the effectiveness of different surgical options in the treatment of nonunion of a femoral shaft fracture after initial intramedullary nailing. DESIGN: Retrospective. SETTING: University hospital. PATIENTS AND METHODS: During a seven-year period a total of 278 skeletally mature patients with 280 fresh femoral shaft fractures were treated by intramedullary nailing. Of these patients, a subgroup of consecutive patients with nonunion of the fracture were subjected to a detailed analysis and were followed until the fracture was united (mean thirty-three months). Injury mechanism, fracture pattern using various established classifications, any possible concomitant injuries, complications, and subsequent surgical interventions were recorded. RESULTS: Of the total of 280 fractures, nonunion was observed in thirty-four patients with thirty-five fractures (12.5 percent). To achieve solid union, one reoperation was sufficient in twenty-five fractures, six fractures had to be operated on twice, and four needed three operations. There were five patients with autogenous bone grafting alone, and all five required a further reoperation for the nonunion. After a dynamization procedure, four of seventeen patients required a further reoperation. After eight exchange nailing procedures, further surgery for nonunion was necessary in only one case. Solid union was achieved within six months after the final successful reoperation. A marked shortening of the femur developed as a local complication in six cases, four of which had undergone dynamization as final treatment before solid union. CONCLUSIONS: Exchange nailing without extracortical bone grafting seems to be the most effective method to treat a disturbed union of a femoral shaft fracture after intramedullary nailing. Autogenous extracortical bone grafting alone proved to be insufficient. Dynamization predisposed to shortening of the bone.