A pathogenic role for brain-derived neurotrophic factor (BDNF) in fibrous dysplasia of bone.

Brain derived neurotrophic factor (BDNF) is a neurotrophin, expressed in the central nervous system and in peripheral tissues, that is regulated by the Gsα/cAMP pathway. In bone, it regulates osteogenesis and stimulates RANKL secretion and osteoclast formation in osteolytic tumors such as Multiple Myeloma. Fibrous dysplasia (FD) of bone is a rare genetic disease of the skeleton caused by gain-of-function mutations of the Gsα gene in which RANKL-dependent enhanced bone resorption is a major cause of bone fragility and clinical morbidity. We observed that BDNF transcripts are expressed in human FD lesions. Specifically, immunolocalization studies performed on biopsies obtained from FD patients revealed the expression of BDNF in osteoblasts and, to a lower extent, in the spindle-shaped cells within the fibrous tissue. Therefore, we hypothesized that BDNF can play a role in the pathogenesis of FD by stimulating RANKL secretion and bone resorption. To test this hypothesis, we used the EF1α-GsαR201C mouse model of the human disease (FD mice). Western blot analysis revealed a higher expression of BDNF in bone segments of FD mice compared to WT mice and the immunolabeling pattern within mouse FD lesions was similar to that observed in human FD. Treatment of FD mice with a monoclonal antibody against BDNF reduced the fibrous tissue along with the number of osteoclasts and osteoblasts within femoral lesions. These results reveal BDNF as a new player in the pathogenesis of FD and a potential molecular mechanism by which osteoclastogenesis may be nourished within FD bone lesions. They also suggest that BDNF inhibition may be a new approach to reduce abnormal bone remodeling in FD.

Changing Treatment Philosophy of Slipped Capital Femoral Epiphysis (SCFE) after Introduction of the Modified Dunn Procedure (MDP): Our Experience with MDP and Its Complications.

BACKGROUND: The modified Dunn procedure (MDP) has become popular during the last 16 years to treat severely displaced slipped capital femoral epiphysis (SCFE) while "in situ" pinning (ISP) has remained valid to treat mild to moderate SCFE, although the indication limit of the Southwick angle (SA) has not yet been established for either procedure. In this context, we reviewed two cohorts of patients with SCFE, one treated by ISP and the other by MDP. We also tried to better elucidate the etiopathogenesis of hip instability, a severe complication of MDP. METHODS: Fifty-one consecutive patients with 62 hips affected by SCFE were treated by us from 2015 to 2019: 48 hips with a SA ≤ 40° had ISP while 14, with the SA > 40°, had MDP. The latter also had a CT scan to better investigate the SCFE morphology. Results were assessed using the Harris Hip Score. RESULTS: The mean length of follow up of the two cohorts was 5.4 years (range: 3 to 8 years). Of the 35 hips operated by ISP with a full follow-up evaluation, 30 had an excellent or good result, 3, fair, and 2, poor. Of the 14 hips that underwent MDP, 11 had an excellent or good result, 1, fair, and 2, poor. A CT scan showed femoro-acetabular incongruency in two unstable hips following MDP. CONCLUSIONS: We performed ISP in chronic SCFE with the SA ≤ 40° and MDP in acute and chronic SCFE with the SA > 40°, with satisfactory results. In both acute-on-chronic and chronic long-lasting SCFE with severe displacement, planned for MDP, a CT scan should be carried out to evaluate possible femoro-acetabular incongruency that may cause hip instability.

Application of Phage Therapy in a Case of a Chronic Hip-Prosthetic Joint Infection due to Pseudomonas aeruginosa: An Italian Real-Life Experience and In Vitro Analysis.

Background: Prosthetic joint infection (PJI) caused by Pseudomonas aeruginosa represents a severe complication in orthopedic surgery. We report the case of a patient with chronic PJI from P. aeruginosa successfully treated with personalized phage therapy (PT) in combination with meropenem. Methods: A 62-year-old woman was affected by a chronic right hip prosthesis infection caused by P. aeruginosa since 2016 . The patient was treated with phage Pa53 (I day 10 mL q8h, then 5 mL q8h via joint drainage for 2 weeks) in association with meropenem (2gr q12h iv) after a surgical procedure. A 2-year clinical follow up was performed. An in vitro bactericidal assay of the phage alone and in combination with meropenem against a 24-hour-old biofilm of bacterial isolate was also carried out. Results: No severe adverse events were observed during PT. Two years after suspension, there were no clinical signs of infection relapse, and a marked leukocyte scan showed no pathological uptake areas. In vitro studies showed that the minimum biofilm eradicating concentration of meropenem was 8 µg/mL. No biofilm eradication was observed at 24 hours incubation with phages alone (108 plaque-forming units [PFU]/mL). However, the addition of meropenem at suberadicating concentration (1 µg/mL) to phages at lower titer (103 PFU/mL) resulted in a synergistic eradication after 24 hours of incubation. Conclusions: Personalized PT, in combination with meropenem, was found to be safe and effective in eradicating P. aeruginosa infection. These data encourage the development of personalized clinical studies aimed at evaluating the efficacy of PT as an adjunct to antibiotic therapy for chronic persistent infections.

Intramedullary Nailing for Lower Limb Polyostotic Fibrous Dysplasia in Children: A Long-term Follow-up Study.

BACKGROUND: In children, intramedullary nailing (IN) has been proposed as the best treatment when the femur and tibia are totally affected by fibrous dysplasia (FD). However, in younger children IN must be repeated to maintain stabilization of the affected skeletal segment during growth. We report the long-term results in a cohort of patients in whom more than two-thirds of cases had IN repeated during growth. METHODS: Twenty-nine femurs and 14 tibias totally affected by FD were treated by IN in 21 patients with polyostotic FD and McCune-Albright syndrome. Thirteen patients with 35 femoral and tibial deformities had a painful limp whereas 8 presented fractures. The patients had their first IN at a mean age of 9.26±2.68 years (range: 4 to 14 y). IN was repeated during growth in the younger patients, and all the patients underwent a mean of 2.13 femoral and 1.50 tibial IN per limb. The last IN was performed at a mean age of 16.42±1.95 years (range: 11 to 19 y). Titanium elastic nails and adult humeral nails were used in younger children, whereas adult femoral cervicodiaphyseal and interlocking tibial nails were used in older children and adolescents. At the latest follow-up, the patients were evaluated with a clinicoradiographic scale. All the data were statistically analyzed. RESULTS: The mean length of follow-up from the last IN was 6.47±3.10 years (range: 3 to 14 y), and the mean age of the patients at follow-up was 22.85±3.53 years (range: 14 to 29 y) when lower limbs were fully grown in all but 1 patient. Satisfactory long-term results were obtained in about 81% of our patients, while complications occurred in 32.5% of the 43 cases. CONCLUSION: Lower limb IN-that was repeated in younger children during growth-provided satisfactory long-term results in most of our patients, with fracture and deformity prevention and pain control, regardless of the high rate of complications that mainly affected the femoral cases. Missing scheduled follow-ups was the main predictor of a poor result. LEVEL OF EVIDENCE: Level IV-case series.

Surgical treatment of slipped capital femoral epiphysis (SCFE) by Dunn procedure modified by Ganz: a systematic review.

BACKGROUND: Treatment of SCFE is still controversial, especially in moderate and severe forms. Dunn osteotomy performed with the Ganz approach became very popular in the last decade, although it is a complicated and challenging surgical procedure with a risk of AVN. The aim of our study was to analyze the current literature verifying the effectiveness of this surgical procedure, with specific attention to the incidence of AVN and other complications. MAIN BODY: A systematic review on the subject was performed according to the PRISMA guidelines. A literature search was performed by searching all published articles about the topic in the databases. The articles were screened for the presence of the following inclusion criteria: patients affected by slipped capital femoral epiphysis (SCFE) surgically treated by Dunn osteotomy using the Ganz surgical approach. All the patients affected by pathologies other than SCFE, treated without surgery or with procedures not including a surgical hip dislocation were excluded. Based on inclusion and exclusion criteria, 23 studies were included in our systematic review. Selected articles were published from 2009 to 2021 and they included 636 overall hips. According to the selected articles, Dunn osteotomy modified by Ganz, performed by an experienced surgeon, allows for anatomical reduction of moderate or severe SCFE with a low incidence of AVN. CONCLUSIONS: The few papers with long term follow-up, reported no progression of hip osteoarthritis, however, since the patients are adolescent at surgery, longer follow-up studies are needed to validate this statement. It is still debated if better results are obtained in stable or unstable SCFE. The indication of this procedure in mild SCFE remains controversial. LEVEL OF EVIDENCE: 3.

Nanostring technology on Fibrous Dysplasia bone biopsies. A pilot study suggesting different histology-related molecular profiles.

Identifying the molecular networks that underlie Fibrous Dysplasia (FD) is key to understand the pathogenesis of the disease, to refine current diagnostic approaches and to develop efficacious therapies. In this study, we used the NanoString nCounter Analysis System to investigate the gene signature of a series of nine Formalin Fixed Decalcified and Paraffin-Embedded (FFDPE) bone biopsies from seven FD patients. We analyzed the expression level of 770 genes. Unsupervised clustering analysis demonstrated partitioning into two clusters with distinct patterns of gene expression. Differentially expressed genes included growth factors, components of the Wnt signaling system, interleukins and some of their cognate receptors, ephrin ligands, matrix metalloproteinases, neurotrophins and genes encoding components of the cAMP-dependent protein kinase. Interestingly, two tissue samples obtained from the same skeletal site of one patient one year apart failed to segregate in the same cluster. Retrospective histological review of the samples revealed different microscopic aspects in the two groups. The results of our pilot study suggest that the genetic signature of FD is heterogeneous and varies according to the histology and, likely, to the age of the lesion. In addition, they show that the Nanostring technology is a valuable tool for molecular translational studies on archival FFDPE material in FD and other rare bone diseases.

Clubfoot pathology in fetus and pathogenesis. A new pathogenetic theory based on pathology, imaging findings and biomechanics-a narrative review.

Several studies have described the pathology of idiopathic congenital clubfoot (ICCF) in fetus. Numerous pathogenetic theories have been postulated on ICCF, but many of them lack any objective evidence. Pathologic studies in fetus together with MRI studies in patients with ICCF seem to favor the theory of a muscular imbalance of the foot activators during fetal growth as the main pathogenetic factor of ICCF. Our objectives were: (I) To support the theory of muscular imbalance as the primary pathogenetic factor of ICCF; (II) To clarify why atrophy and shortening affect the activator muscles of the foot unevenly, as reported by literature. A literature search based on MEDLINE and the COCHRANE database was performed to identify all published studies from 1929 to 2020 which report ICCF pathology in fetus, its etiopathogenesis, and imaging and biomechanical studies showing how the basic pathology may be addressed by Ponseti treatment. A manual search was also performed of the references cited in studies, reviews, and university libraries. Altered size, shape and articular relationships of the tarsal bones, and uneven atrophy and shortening of the leg muscles together with capsule and ligament abnormalities were the main pathologic findings reported in fetus with ICCF. Regarding ICCF pathogenesis, the main debate is between the advocators of a primitive blastemal defect of the tarsal bones leading to the skeletal abnormalities and those who hold that the latter are secondary to a deforming force generated by the soft tissues. Imaging studies have shown that the Ponseti method is able to address the skeletal abnormalities, the correction of which is maintained until adulthood, whereas leg muscle atrophy is not improved but tends to worsen with growth. Preliminary histochemical studies of the soleus-Achilles tendon junction have shown a decrease of the growth factors and the presence of myostatin, both down-regulators of muscle growth in patients with ICCF. The authors postulate that a defect of both the radial and the longitudinal growth unevenly affecting the leg muscles with a consequent imbalance of the foot activators might be the main pathogenetic factor of ICCF. Further studies are needed to confirm this theory.

The effectiveness of preliminary traction in the treatment of congenital dislocation of the hip.

BACKGROUND: Historical papers on the treatment of congenital dislocation of the hip suggest the use of preliminary traction to facilitate closed reduction or to decrease the risk of avascular necrosis (AVN) of the femoral head. In the 1980s, some authors questioned the role of preliminary traction and suspended its use, yielding satisfactory results. Since then, several studies called into question this method, and some authors have continued to recommend preliminary traction while other authors have discouraged its use. MATERIALS AND METHODS: We reanalysed the full set of radiographs of 71 hips (52 patients) surgically treated by a medial approach after 4 weeks of preoperative longitudinal traction. The mean age at operation was 16 months. Before and after traction, the height of the dislocation was graded according to the Gage and Winter method. The hips were divided into two groups: group 1, in which the traction was effective, and group 2, in which the traction was not effective. These two groups were statistically analysed regarding the severity of the dislocation, the age of the patient at surgery and the incidence of AVN. RESULTS: Preliminary traction was effective in 48 hips (68%, group 1), while it was not effective in the remaining 23 (32%, group 2). The effectiveness of preliminary traction was statistically related to the height of the dislocation and to the age of the patient at surgery, with traction being less effective in more severe dislocations and in older children. The incidence of AVN was statistically lower in group 1 than in group 2. CONCLUSIONS: In our study population, despite not having a control group, preliminary traction-when effective-seemed to reduce the incidence of AVN in patients surgically treated for congenital dislocation of the hip. The effectiveness of the traction was influenced by the severity of the dislocation and the age of the patient; it worked better for less severe dislocations and in younger children. To reduce hospital costs, traction should be applied at home. LEVEL OF EVIDENCE: 3.

Surgical Treatment of Severe Idiopathic Flexible Flatfoot by Evans-Mosca Technique in Adolescent Patients: A Long-Term Follow-Up Study.

Flexible idiopathic flatfoot is very common in growing age and rarely causes pain or disability. Surgery is indicated only in severe symptomatic cases that are resistant to conservative treatment, and numerous surgical procedures have been proposed. Lateral column calcaneal lengthening as described by Evans and modified by Mosca is a widely used surgical technique for the correction of severe symptomatic flexible flatfoot. In the present study, we report the long-term clinical and radiographic results in 14 adolescent patients (mean age: 12.8 years) affected by severe symptomatic flexible flatfoot, surgically treated by Evans-Mosca procedure, for a total of 26 treated feet (12 cases bilateral and 2 unilateral). In all cases, surgery was indicated for the presence of significant symptoms resistant to nonsurgical management. Clinical evaluation was made according to the American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, the Foot and Ankle Disability Index (FADI) Score, and Yoo et al.'s criteria. Radiographic evaluation was made using anteroposterior and lateral weight-bearing radiographs of the feet to evaluate Meary's angle and Costa-Bertani's angle and to evaluate possible osteoarthritic changes in the midtarsal joints. At follow-up (mean: 7 years and 7 months), we observed a satisfactory result in all patients. The mean average score of the AOFAS Ankle-Hindfoot Scale improved from 60.03 points to 95.26; the mean FADI score improved from 71.41 to 97.44; and according to Yoo et al.'s criteria, the average clinical outcome score was 10.96. At radiographic examination, nonunion of the calcaneal osteotomy was never observed. Meary's angle improved from an average preoperative value of 25° to 1.38° at follow-up; Costa-Bertani's angle improved from an average preoperative value of 154.2° to 130.9° at follow-up. In no case, significant radiographic signs of midtarsal joint arthritis were observed. According to our results, we believe that Evans-Mosca technique is a valid option of surgical treatment for severe idiopathic flexible flatfoot and allows a satisfactory correction of the deformity with a low rate of complications.

Lower limb lengthening over an intramedullary nail: a long-term follow-up study of 28 cases.

BACKGROUND: Limb lengthening using an external fixator requires a long period of external fixation and may be associated with several complications such as axial deformity, fracture of the regenerated bone, and joint stiffness. With the goal of reducing the time of external fixation as well as some of these complications, we performed femoral or tibial lengthening over an intramedullary nail, according to Paley's technique, in 28 patients, followed up after a mean period of 8 years. MATERIALS AND METHODS: Twenty-eight patients treated for lower limb discrepancy by limb lengthening over an intramedullary nail were reviewed from 5 to 11 years after healing of regenerated bone. There were 20 femurs and 8 tibiae, with average age at surgery of 14.2 years and average length inequality of 6.1 cm for femurs and 5.3 cm for tibiae. RESULTS: The mean lengthening was 5.8 cm for femurs and 4.8 cm for tibiae. The mean period of radiographic consolidation of the regenerated bone was 6 months for femoral lengthening and 4.5 months for tibial lengthening. At follow-up, we observed 8 excellent results, 15 good results, 4 fair results, and 1 poor result, based on Paley's evaluation criteria. The main complications were one deep infection, one nonunion of the distracted segment, one breakage of the distal fiche of the external fixator, and one breakage of both distal locking screws of the intramedullary nail. DISCUSSION: We believe that limb lengthening over an intramedullary nail still represents a good method to treat limb length discrepancy because it reduces the time of external fixation, prevents axial deformities and fractures of regenerated bone, and allows early rehabilitation. The new intramedullary lengthening nails, which theoretically are the ideal device for treating limb length inequality, are still very expensive and need longer follow-up for definitive evaluation. LEVEL OF EVIDENCE: 4.

Tönnis triple pelvic osteotomy for the management of late residual acetabular dysplasia: mid-term to long-term follow-up study of 54 patients.

The authors reviewed 54 (58 hips) patients with acetabular dysplasia following developmental dislocation of the hip (DDH), treated by triple pelvic osteotomy according to the Tönnis technique. The aim of our study was to report the long-term clinical and radiographic results of the operation at a mean follow-up of 12 years (from 7 to 20). At diagnosis, all the hips were painful, the Wiberg angle measured less than 20°, and no radiographic signs of osteoarthritis were present. At follow-up, 82.7% of the operated hips showed either excellent or good results, according to Harris, and the Wiberg angle measured an average of 34° (from 26° to 45°). We encountered five complications: one acetabular malrotation and four asymptomatic ischial nonunions. In conclusion, we believe that, although Bernese periacetabular osteotomy is nowadays considered the gold standard for the surgical treatment of the dysplastic hip following DDH, Tönnis osteotomy represents a good treatment option: it is technically easy, enables direct visualization of the three osteotomies, leads to few complications, and its learning curve is short. The absence of radiographic signs of osteoarthritis and hip congruency before surgery are the basic requirements to achieve a successful result.

Complex iatrogenic clubfoot: is it a real entity?

In our study, we aimed to demonstrate whether a complex iatrogenic clubfoot really exists; identify the causative mechanisms; and determine the outcome if properly treated. We observed 54 clubfeet previously treated unsuccessfully by manipulation and casting elsewhere. All the feet had been classified at diagnosis as typical clubfeet. In 26 cases, the cast had slipped down, entrapping the foot in a plantar-flexed position. Nine clubfeet out of those 26 cases presented the clinical features of a complex iatrogenic deformity. These were treated with the modified Ponseti protocol and evaluated at follow-up according to the International Clubfoot Study Group Score. The length of follow-up averaged 7.2 years. Two feet showed an excellent result, five feet showed a good result, and two feet showed a fair result. The relapse rate was 55% in complex clubfeet. Relapsed clubfeet were treated by Achilles tenotomy or lengthening and anterior tibial tendon transfer. We believe that faulty manipulation and a poor casting technique may convert a typical clubfoot into a complex iatrogenic deformity. Risk factors include severe clubfoot, short and stubby foot, and unmolded casts slipping down.

Intraoperative Disinfection by Pulse Irrigation with Povidone-Iodine Solution in Spine Surgery.

BACKGROUND: Deep wound infection in spine surgery is a debilitating complication for patients and increases costs. The objective of this prospective study was to evaluate the efficacy of wound pulse irrigation with a dilute povidone-iodine solution in the prevention of surgical site infection. METHODS: 50 patients undergoing spinal surgery were randomly divided into two groups (A and B) of 25 patients each. In group A, wounds were irrigated with dilute (3%) povidone-iodine solution through a low-pressure pulsatile device. In group B, wounds were irrigated with saline solution through a bulb syringe. In both groups, specimens for bacterial culture were harvested from surgical site before and after irrigation. RESULTS: In group A, no surgical site infection occurred; in group B, deep wound infection was observed in 3 patients. In both groups, before irrigation some cultures have been found positive for bacterial contamination. CONCLUSION: Our study seems to support the idea that low-pressure pulsating lavage of surgical wounds with povidone-iodine diluted to a nontoxic concentration of 3% is an effective therapeutic adjunct measure to prevent surgical site infection in spine surgery. However, the number of the enrolled patients is small and a significant statistical analysis is not practicable. This trial is registered with NCT03249363.

Bisphosphonate-induced zebra lines in fibrous dysplasia of bone: histo-radiographic correlation in a case of McCune-Albright syndrome.

Bisphosphonates (BPs) are currently used in the treatment of diverse bone diseases including fibrous dysplasia of bone (FD). In pediatric patients, a radiographic consequence of cyclical administration of BPs is the development of apo-, epi-, and meta-physeal sclerotic bands, otherwise known as zebra lines, which result from the temporary inhibition of osteoclastic activity at the time of drug treatment. We report here on a child with McCune-Albright syndrome (FD in addition to hyperfunctioning endocrinopathies and skin hyperpigmentation) treated with cyclical intravenous infusions of pamidronate in which conventional radiography, contact microradiography, histology, and backscattered electron image analysis demonstrated that zebra lines formed only where bone was normal, were arrested at the boundary between FD-unaffected and FD-affected bone where bone is sclerotic, and were absent within the undermineralized FD bone. Moreover, in spite of the treatment, the FD lesions continued to expand. This case report is unique because no previously published studies correlated the radiographic and the histologic features of BP-induced zebra lines in the metaphysis of an FD-affected long bone of the limbs.

A unique case of multiple non-ossifying fibromas with polyostotic monomelic distribution and aggressive clinical course.

Multiple non-ossifying fibromas (MNOFs) occur either isolated or in association with other anomalies, are usually localized in the long bones of the lower limbs, may be radiographically confused with other skeletal lesions, and tend to heal spontaneously with the completion of the skeletal growth. Segmental distribution, either monomelic or polymelic and ipsilateral, is rare and commonly observed in the context of developmental diseases known as "RASopathies", which are caused by mutations in genes that encode components or regulators within the Ras/mitogen-activated protein kinase signaling pathway. We describe here the radiographic and pathologic features of an 18-year-old Caucasian boy, whose clinical history started at the age of 3 when the diagnosis of aneurysmal bone cyst was made on a lytic lesion of his left clavicle. Over the following 2 years, the patient developed polyostotic and monomelic lesions within the left humerus, radius, and ulna. No other skeletal and extra-skeletal anomalies were clinically detected. The lesions were interpreted as consistent with polyostotic fibrous dysplasia and MNOFs and showed an unusually aggressive clinical course with progressive increase in size and coalescence. The definitive diagnosis of MNOFs was made after the exclusion of fibrous dysplasia by molecular analysis. The polyostotic and monomelic distribution of the lesions and the unusually aggressive clinical course contribute to make this case of MNOFs unique.

Ponseti Treatment of Rigid Residual Deformity in Congenital Clubfoot After Walking Age.

BACKGROUND: There is no established treatment for rigid residual deformity of congenital clubfoot (CCF) after walking age. Soft-tissue procedures, osseous procedures, and external fixation have been performed with unpredictable results. We applied the Ponseti method to patients with this condition in order to improve the outcomes of treatment. METHODS: We retrospectively reviewed the cases of 44 patients (68 feet) with congenital clubfoot whose mean age (and standard deviation) at treatment was 4.8 ± 1.6 years. All patients had been previously treated in other institutions by various conservative and surgical protocols. Residual deformity was evaluated using the International Clubfoot Study Group Score (ICFSGS), and stiffness was rated by the number of casts needed for deformity correction. Ponseti manipulation and cast application was performed. Equinus was usually treated with percutaneous heel-cord surgery, while the cavus deformity was treated with percutaneous fasciotomy when needed. Tibialis anterior tendon transfer (TATT) was performed in patients over 3 years old. At the time of follow-up, the results were evaluated using the ICFSGS. RESULTS: Before treatment, 12 feet were graded as fair and 56, as poor. Two to 4 casts were applied, with each cast worn for 4 weeks. Stiffness was moderate (2 casts) in 23 feet, severe (3 casts) in 30 feet, and very severe (4 casts) in 15 feet. Percutaneous heel-cord surgery was performed in 28 feet; open posterior release, in 5 feet; plantar fasciotomy, in 30 feet; and TATT, in 60 feet. The mean length of follow-up was 4.9 ± 1.8 years. Eight feet had an excellent result; 49 feet, a good result; and 11 feet, a fair result. No patient had pain. All of the feet showed significant improvement. CONCLUSIONS: Ponseti treatment with TATT, which was performed in 88% of the feet, was effective, and satisfactory results were achieved in 84% of the feet. At the time of follow-up, no patient showed an abnormal gait, all feet were plantigrade and flexible, but 2 feet (2.9%) had relapsed. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Treatment of recalcitrant atrophic non-union of the humeral shaft with BMP-7, autologous bone graft and hydroxyapatite pellets.

Recalcitrant humeral non-union is a disabling condition that is extremely difficult to treat. The use of BMP-7 has been proposed to improve bone healing. This is a report of the results obtained in 12 patients with recalcitrant humeral non-union treated using stable fixation with a long locking compression plate and BMP-7, autologous bone graft and hydroxyapatite pellets applied at the non-union site. Patients had up to three surgical attempts at non-union healing prior to our treatment. The average time from the initial fracture to our surgery was 5.2 years. Average follow-up was 5.3 years. At follow-up, non-union had healed in all patients by an average of 7.3 months. All the patients were very satisfied with their final results, despite a restricted range of motion of the elbow and a moderate muscular atrophy, which was frequently observed. Our study shows that BMP-7 associated with autologous bone grafting and hydroxyapatite pellets after stable fixation is an effective adjuvant to stimulate bone healing in the treatment of recalcitrant humeral non-union.

Two-Stage Surgical Treatment of Complex Femoral Deformities with Severe Coxa Vara in Polyostotic Fibrous Dysplasia.

INTRODUCTION: For complex femoral deformities in patients affected by polyostotic fibrous dysplasia and coxa vara associated with shepherd's crook deformity of the femoral shaft, the correct treatment is stabilization with an interlocking cervicodiaphyseal nail after correction of all of the femoral deformities. STEP 1 THE FIRST-STAGE PROCEDURE­INTERTROCHANTERIC VALGUS OSTEOTOMY AND FIXATION WITH A HIP BLADE-PLATE PREOPERATIVE PLANNING: Evaluate the patient radiographically and select the hardware. STEP 2 PATIENT PREPARATION: Position the patient on the traction table. STEP 3 PREPARATION OF THE LATERAL ASPECT OF THE PROXIMAL PART OF THE FEMUR AND MARKING THE POSITION FOR BOTH THE OSTEOTOMY AND THE HIP BLADE-PLATE: Expose the lateral aspect of the proximal part of the femur and mark the position of both the blade-plate and the osteotomy. STEP 4 BLADE-PLATE POSITIONING OSTEOTOMY AND OSTEOTOMY FIXATION: Prepare the slot for the blade, perform the osteotomy, and correct the valgus alignment of the proximal part of the femur. STEP 5 POSTOPERATIVE MANAGEMENT: Check postoperative bleeding, provide blood transfusions if needed, and have the patient resume walking. STEP 6 THE SECOND-STAGE PROCEDURE­HIP PLATE REMOVAL OSTEOTOMY OF THE FEMORAL SHAFT TO CORRECT THE SHEPHERD'S CROOK DEFORMITY AND STABILIZATION WITH A CERVICODIAPHYSEAL NAIL PREOPERATIVE PLANNING: Study the patient radiographically, simulate the osteotomies, perform another assessment of lower-limb length, and select the hardware. STEP 7 PATIENT PREPARATION PLATE REMOVAL AND DRILLING OF KIRSCHNER WIRES TO MARK THE SITE OF THE PLANNED OSTEOTOMIES: Position the patient on the traction table and expose the lateral aspect of the femur from the tip of the greater trochanter to the level of the most distal planned osteotomy. STEP 8 PERFORM ALL OF THE OSTEOTOMIES AND DRILL A MEDULLARY CANAL IN THE OSTEOTOMY FRAGMENTS: All of the osteotomies are performed, and a medullary canal is drilled in each femoral fragment. STEP 9 NAIL AND SPIRAL BLADE INSERTION STABILIZATION OF OSTEOTOMIES AND CLOSURE: Introduce the nail into the osteotomy fragments and insert the spiral blade and distal locking screws. STEP 10 POSTOPERATIVE MANAGEMENT: Check postoperative bleeding, which is usually marked; administer blood transfusions as needed; and have the patient resume walking. RESULTS: We performed this surgery on 13 femora in 11 patients.

Changing Pattern of Femoral Deformity During Growth in Polyostotic Fibrous Dysplasia of the Bone: An Analysis of 46 Cases.

BACKGROUND: In polyostotic fibrous dysplasia (PFD) affecting the femur, 6 types of stable femoral deformities have been identified, ranging from the mild type 1 to the most severe type 6. The purpose of our study was to identify the type of deformity present at diagnosis in children with PFD affecting the femur, and to investigate possible changes in the original type with growth. METHODS: Twenty-seven children affected by either PFD or McCune-Albright syndrome, with 46 affected femurs, were consecutively observed from 1994 to 2010. Radiographs of the pelvis and femurs were taken at diagnosis, and afterward at regular intervals of 6 to 12 months depending on the clinical evolution of each case. Radiographs of the femurs taken at 3 and 7 years after diagnosis were selected to assess the evolution of the femoral deformity. Deformities were classified according to the femoral shape, neck-shaft angle value, and the presence of shepherd's crook deformity evaluated on AP radiographs. RESULTS: The average age of the patients at diagnosis was 5 years (range, 2 to 11 y). At diagnosis, 30 femurs were type 1; 12, type 2; 1, type 3; 1, type 4; and 2, type 5. Three years later, 39% of the femurs had maintained the original deformity present at diagnosis, whereas only 13% did so 7 years after diagnosis.Predictors of change to a more severe type were: younger age at diagnosis, McCune-Albright syndrome, rapid spreading of fibrodysplastic tissue from the trochanteric area to the proximal femoral shaft, cortical thinning of the proximal femur, calcar osteolysis, and presence of an intertrochanteric cystic-like lesion eroding the calcar. CONCLUSIONS: In children with PFD affecting the femur, 61% of the femoral deformity present at diagnosis switched to a more severe type of deformity within 3 years from diagnosis, whereas 87% either shifted to a more severe type of deformity or already had corrective surgery within 7 years after diagnosis. LEVEL OF EVIDENCE: Level IV.