Management of Pediatric Type I Open Fractures in the Emergency Department or Operating Room: A Multicenter Perspective.

BACKGROUND: The management of pediatric type I open fractures remains controversial. The aim of this study is to compare outcomes in type I open fractures managed with superficial wound debridement and antibiotics in the emergency department (ED) (nonoperative management) to patients managed with operative debridement and antibiotics (operative management). METHODS: A multicenter retrospective review was performed of all pediatric type I open forearm, wrist, and tibia fractures treated at 4 high volume pediatric centers between 2000 and 2015. Patients with multiple traumatic injuries, immunocompromised patients, or those without final radiographs indicating healing were excluded. RESULTS: In total, 219 patients met inclusion criteria. A total of 170 fractures were treated operatively (77.6%), 49 fractures were treated nonoperatively (22.4%). There was 1 infection in the nonoperative group (2.0% infection rate), and no infections in the operatively managed group (P=0.062). Cefazolin was the most commonly administered antibiotic (88.1% of patients). Duration of hospital-administered antibiotics was significantly different, with a mean of 10.9 hours in the nonoperative group and 41.6 hours in the operative group (P<0.001). Length of stay averaged 16.3 hours for nonoperative patients and 48.6 hours for the operatively treated patients (P<0.001). In the nonoperative group, 44/49 had documented superficial wound debridement in the ED utilizing, on an average, 1500 mL of irrigant. There were 10 other complications, 9 in the operative group (5.4%) and 2 in the nonoperative group (4.1%, P=0.107), including 2 compartment syndromes and 1 acute carpal tunnel syndrome all requiring immediate surgical release (1.8%) in the operative group. CONCLUSIONS: There was no significant difference in infection rate or complication rate in those managed with antibiotics and operative debridement versus those managed with superficial wound debridement and antibiotics in the ED. Consideration should be given to the similar safety profiles for these 2 treatment modalities when managing pediatric patients with type I open fractures. LEVEL OF EVIDENCE: Level III.

Severity of Asynchronous Slipped Capital Femoral Epiphyses in Skeletally Immature Versus More Skeletally Mature Patients.

BACKGROUND: Routine prophylactic screw fixation for skeletally immature patients with slipped capital femoral epiphysis (SCFE) continues to be debated. The purpose of this study was to assess the slip severity of a second SCFE in skeletally immature versus more mature patients and determine necessity of contralateral hip prophylactic screw fixation. METHODS: All patients treated for SCFE at 3 pediatric hospitals over a 10-year time period (January 1, 2002 to December 31, 2011) were evaluated. Patients were included if they had a unilateral SCFE and a contralateral asynchronous SCFE, and were divided into immature (Oxford triradiate score 1) versus more mature (Oxford triradiate score 2 and 3) groups. Data evaluation included age, time between slips, body mass index, Southwick angles of first then second SCFEs, and follow-up duration. RESULTS: There were a total of 45 patients: 16 patients in the skeletally immature and 29 patients in the more mature group. Average age at first SCFE in immature patients was 10.9 years and in more mature patients 12.1 years (P=0.70). Age at second SCFE in immature patients was 11.5 years and in more mature patients 13.0 years (P=0.023). Average time between SCFEs was 6.6 months for immature and 11.4 months for more mature patients (P=0.093). Southwick angles for immature patient first and second SCFEs were 25 and 12.9 degrees, respectively, and for more mature patient first and second SCFEs were 31 and 21 degrees, respectively. Southwick angles were higher at first and second slips in the more mature group, significant only at the second slip (P=0.032). SCFE severity at initial event was predictive of severity of second SCFE regardless of maturity (P=0.043). Regression analysis of slip severity against multiple patient factors demonstrated triradiate score was not a factor assessing subsequent SCFE magnitude (P=0.099). CONCLUSIONS: There was no significant difference between first and second SCFEs regardless of skeletal maturity but severity of initial SCFE did correlate with severity of the second SCFE. Deciding not to prophylactically pin an unaffected hip does not lead to worse deformity if a second SCFE occurs in skeletally immature or more mature patients, unless the initial event is severe. Prophylactic pin fixation in skeletally immature patients should occur as a shared decision between patient, guardians, and treating surgeon. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

A Modification to the McHale Procedure Reduces Operative Time and Blood Loss.

BACKGROUND: Treatment of symptomatic spastic hip dislocations in adolescent patients with cerebral palsy includes a variety of described salvage type procedures. In 1990, McHale and colleagues described a technique involving a femoral head resection, valgus-producing proximal femoral osteotomy, and advancement of the lesser trochanter into the acetabulum. We have modified this technique in 3 ways by: performing it in the lateral position with a more posterior approach, not advancing the lesser trochanter into the acetabulum, and closing the capsule over the acetabulum. The purpose of this paper is to describe our technique and to compare the results to Castle type procedures and McHale procedures performed as originally described. METHODS: We retrospectively reviewed all salvage type procedures performed at our institution for spastic hip dislocations in children with cerebral palsy from 2003 to 2013. Preoperative and postoperative pain, estimated blood loss, operative time, length of stay in the hospital, and postoperative pelvis radiographs were reviewed for heterotopic ossification formation and proximal femoral migration. RESULTS: Twenty-six patients with 30 hip procedures were reviewed. The modified McHale technique had shorter operative times when compared with the supine McHale technique and the Castle procedure (134, 171, and 139 min, respectively). There was a trend toward less blood loss in the modified McHale technique, but this was not significant. There was no difference in length of stay in the hospital. The majority of McHale patients (>63%) had pain relief postoperatively, where half of the Castle patients required a revision surgery for pain (4 of 8). There was less heterotopic ossification seen in the modified McHale technique (6.25%) when compared with supine McHale and Castle techniques (both 50%). However, there was more proximal femoral migration in the modified McHale group. CONCLUSIONS: The modified McHale technique is faster with otherwise equivocal results in the immediate operative periods. There is less heterotopic bone formation but more proximal femoral migration with this new technique. LEVEL OF EVIDENCE: Level IV-case series.

Calf circumference discrepancies in patients with unilateral clubfoot: Ponseti versus surgical release.

BACKGROUND: Talipes equinovarus is the most common congenital lower limb abnormality. Decreased calf size has been found to have negative impacts on patients' subjective appraisals of long-term outcomes. This study compares calf circumference ratios in 2 groups of patients with unilateral clubfoot, those treated according to the Ponseti method and those treated with extensive surgery, to determine whether the current standard of care achieves better anatomic outcomes. METHODS: Patients >1 year after treatment for unilateral clubfoot were recruited during normal follow-up appointments and both calves were measured using a standardized protocol. A questionnaire concerning their treatment history was also completed. Data were analyzed by comparing calf circumference ratios between treatment modalities. RESULTS: Thirty-five patients with unilateral clubfoot were recruited after satisfying inclusion criteria. Twenty-four (69%) were included in the Ponseti-managed group, and 11 (31%) were in the extensive surgery group. The affected legs were on average 3% to 10% smaller than the control legs across all groups. The surgery group's average calf ratio was significantly less at 90.8%±3.5% compared with 94.4%±3.3% in the Ponseti group. CONCLUSIONS: The calf circumference of limbs affected by clubfoot is significantly smaller in those treated with extensive surgery as compared with those treated with the Ponseti method alone, with or without percutaneous tenotomy. This supports the Ponseti method as the standard of care for achieving the most favorable anatomic outcome. LEVEL OF EVIDENCE: Level I.

Distal femoral physeal fixation: are smooth pins really safe?

BACKGROUND: Distal femoral physeal fractures have a high incidence of physeal arrest. Several factors have been postulated to contribute to this high incidence, including fracture type, displacement, the undulating nature of the physis, and fracture reduction/fixation. The purpose of this study was to determine whether the position of percutaneous smooth pins across the physis contributes to physeal bar formation. METHODS: The previously validated New Zealand white rabbit model was used. Power analysis determined that 30 animals were required. All animals had a constant 0.045 smooth Kirschner (K) wire placed under fluoroscopic guidance from the distal lateral femur across the physis centrally. A second 0.045 K-wire was placed in a cross-pin configuration from the medial side in one of 2 positions: zone 1--crossing the physis centrally or zone 2--crossing the physis peripherally. Pins were removed after 4 weeks and micro computed tomography was performed at 8 weeks to assess for physeal bar formation. Histologic analysis was performed to confirm bar formation. RESULTS: Two physeal bars (7%) were seen after removal of the constant (lateral pin). The peripheral pin resulted in bar formation in 2 animals (13%) and the central pin in 1 animal (7%). A χ² test was performed; there was no statistically significant difference between zones in terms of bar formation (P=0.5428). CONCLUSIONS: Injury to the growth plate after distal femoral fracture may be unavoidable. Treatment is aimed to minimize further injury to the physis. Cross-pinning with smooth K-wires results in a low rate of physeal injury. Pins that cross the physis both centrally and peripherally appear to have the same risk for physeal bar formation. CLINICAL RELEVANCE: This study reveals that physeal bar formation can be seen with smaller than previously reported cross-sectional damage to the distal femoral physis. This study highlights the need to carefully select and perform fixation of the distal femoral physis with as little additional trauma to the physis as possible.

Reliability of measurements of clavicle shaft fracture shortening in adolescents.

BACKGROUND: A relative indication for surgical treatment of midshaft clavicle fractures is shortening ≥2.0 cm. A standard method for determining shortening with routine clavicle radiographs has not been established. This study evaluated the interobserver and intraobserver reliability when measuring shortening of midshaft clavicle fractures in adolescents. METHODS: We identified all clavicle radiographs of simple midshaft clavicle fractures in adolescents from 2006 to 2010. Thirty-two radiographs were chosen following a power analysis for 7 observers. Each film was measured twice by each evaluator using 2 separate methods. Method 1 was the evaluator's method of choice to determine shortening on the digital radiographs. Method 2 was standardized. Intraclass correlation coefficient and confidence intervals (CI) were calculated to determine interrater reliability, and average differences between the 2 time points with 95% CI were calculated to determine intrarater reliability. RESULTS: Interrater reliability for method 1 was 0.771 (95% CI, 0.655-0.865) and 0.743 (95% CI, 0.604-0.851) at the 2 time points for fair agreement. Interrater reliability for method 2 was 0.741 (95% CI, 0.629-0.842) and 0.685 (95% CI, 0.554-0.805) at the 2 time points, for fair and poor agreement, respectively. Neither method was statistically superior to the other. For method 1, the SD for the measurements averaged 3.1 mm. For method 2, the average SD was 3.0 mm. Intrarater reliability for method 1 was 2.62 mm average difference between the 2 time points (95% CI, 2.24-3.00), and for method 2 it was 3.34 mm average (95% CI, 2.88-3.80). Method 2 had a significantly greater difference at the 2 time points than method 1 (P=0.027). CONCLUSIONS: There is only fair agreement among observers when measuring the shortening of clavicle fractures in adolescents on digital clavicle radiographs by either method described. However, as the average difference among measurers was only 3 mm, this is unlikely to influence clinical decision making. A lack of standardization of measurement in previous studies on clavicle fracture treatment may not represent a significant problem. LEVEL OF EVIDENCE: Level III diagnostic study.

Musculoskeletal care of the hemophiliac patient.

Hemophilia is caused by a deficiency of clotting factor VIII or IX and is inherited by a sex-linked recessive pattern. von Willebrand disease, a common, moderate bleeding disorder, is caused by a quantitative or qualitative protein deficiency of von Willebrand factor and is inherited in an autosomal dominant or recessive manner. The most important clinical strategy for the management of patients with hemophilia is the avoidance of recurrent hemarthrosis by continuous, intravenous hematologic prophylaxis. Early hemarthrosis should be aggressively managed with aspiration and clotting factor concentrate until the joint examination is normal. Starting prophylactic factor replacement in infancy may prevent chronic synovitis and arthropathy. The natural history of poorly controlled disease is polyarticular hemophilic arthropathy; functional prognosis is poor. Patients with chronic synovitis may be treated effectively with radiosynovectomy; those who develop joint surface erosions may require realignment osteotomies, joint arthroplasty, and treatment of pseudotumors. Reconstructive surgery for hemophilic arthropathy, especially in patients with factor inhibitor, requires careful hematologic management by an experienced, multidisciplinary team.

A comparison of hip dislocation rates and hip containment procedures after selective dorsal rhizotomy versus intrathecal baclofen pump insertion in nonambulatory cerebral palsy patients.

BACKGROUND: Spasticity is the major etiology for hip dislocation in nonambulatory cerebral palsy patients. Selective dorsal rhizotomy (SDR) was used to control lower extremity spasticity, but is now done infrequently in nonambulatory cerebral palsy. Current surgical treatment is usually intrathecal baclofen pump (ITBP) placement. A major theoretical difference between SDR and ITBP is the effect on the iliopsoas through the L1 nerve root. This study compares the rate of hip dislocation and the need for further hip surgeries in SDR and ITBP patients. METHODS: All nonambulatory cerebral palsy patients who had either an SDR or ITBP and had minimum follow-up of 2 years were retrospectively reviewed for demographic data and timing, total number, and type of hip procedures (soft tissue vs. bony), and occurrence of hip dislocation. χ (2)test was used to assess for statistical significance. RESULTS: Sixty-nine patients who underwent SDR (40 males) and 50 patients who underwent ITBP (27 males) were included in the study. Average age at spasticity intervention was 6 years 11 months for SDR and 9 years 8 months for ITBP. In the SDR group, 25% of hips underwent reconstruction versus 32% of hips in the ITBP group. There were a total of 19 hip procedures in the SDR group and 20 in the ITBP group (P = 0.15). Seventeen soft-tissue procedures were performed in both SDR and ITBP groups (P = 0.265). Six bony procedures (0 salvage) were performed in the SDR group and 10 in the ITBP group (4 salvage; P = 0.075). At final follow-up the hip dislocation rate was 10.6% in the SDR group and 7.4% in the ITBP group. CONCLUSIONS: There was no significant difference in the rate of secondary hip reconstructive surgery or dislocation between nonambulatory cerebral palsy patients who underwent SDR versus ITBP. Reconstruction was required for 25% to 32% of hips despite spasticity intervention with either procedure. This suggests that the L1 nerve root alone does not play a major role in the progression of hip dislocation. LEVEL OF EVIDENCE: Level 3--therapeutic study.

Combined Tillaux and Bimalleolar Ankle Fracture in a Pediatric Patient: A Case Report.

Adolescents are at risk of unique ankle fracture patterns due to closing physes. Transitional ankle fractures, in particular, are an entity specific to adolescent patients due to the asymmetrically open distal tibia physis. Transitional ankle fractures are rarely seen in combination with bimalleolar ankle fracture patterns. This case is of interest because the combined fracture pattern and the treatment method presented have not been previously reported in the literature to our knowledge. A 15-year-old female presented with right ankle pain after a fall while roller skating. Imaging demonstrated a right Tillaux fracture with ipsilateral displaced medial malleolus fracture and minimally displaced Weber C distal fibula fracture. The Tillaux fracture and medial malleolus fractures were treated with open reduction and internal fixation with partially threaded compression screws. The lateral malleolus remained minimally displaced and did not require operative fixation. The patient healed well with no complications. Transitional injuries of the ankle in adolescents have been reported in the literature; however, combined injuries are uncommon and lack representation in the current literature base. These combined injuries are important to be aware of, as missed injuries can result in long-term pain and disability.

Ossifying lipoma of c1-c2 in an adolescent.

BACKGROUND: Ossifying lipomas, characterized by their independence of bony connection to the skeleton, are extremely rare benign neoplasms. They have primarily been described in adults older than 50 years of age and occur in the head and neck region. The etiology is unknown. Excision is the preferred treatment. The objective of this study is to report the case of a rare ossifying lipoma immediately anterior to C1 to C2, requiring a transoral approach for excision. METHODS: The case of an adolescent with a retropharyngeal mass is described. RESULTS: A 15-year-old female patient presented with an asymptomatic parapharyngeal mass detected on routine physical examination. Computed tomography and magnetic resonance imaging noted a calcified, left-sided, parapharyngeal mass, approximately 3×2×2 cm, anterior to C1 and C2, most consistent with a benign osseous lesion. A transoral approach was used to excise the mass. Histologic examination demonstrated an ossifying lipoma. Postoperative imaging confirmed complete excision. The postoperative course was unremarkable, and the patient has had no recurrence at 6-month follow-up. CONCLUSIONS: This case demonstrates that a transoral approach to a lesion anterior to C1 to C2 in an adolescent can be safe, complete, and effective. LEVEL OF EVIDENCE: Case Report, level 5.

Pelvic Avulsion Injuries in the Adolescent Athlete.

Pelvic avulsion fractures are common in youth athletes; many of these injuries can be treated conservatively. This article reviews the etiology, presentation, and management of the more common pelvic avulsion fractures, including anterior superior iliac spine, anterior inferior iliac spine, ischial tuberosity, and iliac crest avulsions. Adolescent pelvic avulsion fractures rely on the amount of fracture displacement to guide treatment. Conservative management includes rest and avoiding use of the muscle(s) that attach to the avulsed fragment. Operative treatment is reserved for widely displaced fractures or symptomatic nonunions. With appropriate treatment, young athletes frequently return to their same level of sport.

Assessment of synovial fluid and serum cytokine levels in children with septic arthritis.

Acute septic arthritis (ASA) is a common orthopedic infection of children which may produce devastating sequelae and chronic morbidity. Improved understanding of the intra-articular inflammatory response in ASA may identify cytokine targets with diagnostic or therapeutic potential, though no detailed investigations to this end have been performed. Given this, we used a multiplex cytokine assay for assessment of levels of 40 different cytokines in the synovial fluid and blood of children with ASA. Twelve children (8 controls undergoing orthopedic surgery for non-infectious conditions and 4 with ASA) were prospectively enrolled. Blood and synovial fluid were collected intraoperatively from each subject, and the levels of 40 cytokines were determined using a multiplex assay. Cytokines were organized by function and structure into 12 groups for analysis. The Benjamini-Hochberg method was used to control for type 1 errors, with an a priori false discovery rate of 10%. Subjects with ASA were younger than controls (mean age 8.0 vs 13.1 years, p=0.0400). Significant elevations were seen in interleukins (IL) with chemokine properties, IL-6 and those in the common-γ chain group in the blood and synovial fluid of children with ASA compared with controls, while significant elevations in 5 additional cytokine groups were seen in synovial fluid from children with ASA compared with controls, most notably IL-6 (median 8294.3 vs 10.7 pg/mL, p=0.0066). Our pilot study is the first to describe in detail the cytokine response in children with ASA, and highlights the need for additional study.

Nosocomial Chronic Osteomyelitis of the Tibia in an Otherwise Healthy Adolescent: A Case Report.

INTRODUCTION: Pseudomonas osteomyelitis in otherwise healthy children is rare but may present following puncture wounds to the foot or involve the skull following mastoiditis. We present a case of nosocomial chronic osteomyelitis of the tibia caused by Pseudomonas in a previously healthy adolescent following surgical debridement of a non-pseudomonal chronic osteomyelitis in the same location 18 months prior. To our knowledge, such a case has not previously been described. CASE REPORT: A 17-year-old previously healthy young man presented with several month duration of pain in the right leg below the knee with no prior trauma, overlying a site of chronic, culture-negative osteomyelitis which was successfully treated with anti-staphylococcal therapy 1year prior. Magnetic resonance imaging of the affected area revealed findings consistent with chronic osteomyelitis at his prior surgical site, while operative culture demonstrated growth of a multidrug-resistant Pseudomonas aeruginosa. An extensive immunological evaluation was unremarkable. He demonstrated clinical and radiographic improvement following 4 months of intravenous antimicrobial therapy. CONCLUSION: Given the extreme rarity of P.aeruginosa in community-acquired osteoarticular infections, as well as the antimicrobial resistance profile demonstrated and the localization to a prior surgical site, this is felt to be the first description of a nosocomial osteoarticular infection with this organism in an otherwise healthy child. Providers should be aware of the potential for osteoarticular infection with atypical organisms in the post-operative patient.

Outcomes of salvage hip surgery in children with cerebral palsy.

This study compared the outcomes of four salvage procedures in treating painful dislocated hips in patients with cerebral palsy: Schanz osteotomy, Girdlestone, Castle, and McHale procedures. A retrospective review of cerebral palsy patients treated between 1990 and 2014 with minimum 6-month follow-up was carried out. Of 69 hips (62 patients), there were 36 McHales, 24 Castles, four Girdlestones, and five Schanz procedures at a mean age of 13.9 years. All four procedures provided pain relief. Proximal femoral migration was similar following the procedures, but heterotopic ossification was more common after the Castle procedure. Bone resorption and revision surgery were more frequent after the McHale procedure.

Treatment of distal femur and proximal tibia fractures with external fixation followed by planned conversion to internal fixation.

PURPOSE: To evaluate healing rates and complications in patients treated with temporary external fixation (EF) and subsequent open reduction and internal fixation (ORIF) for high-energy distal femur or proximal tibia fractures. METHODS: Retrospective analysis of prospectively collected data 1999 to 2005. Demographic data and injury severity score were obtained from medical records. Factors reviewed included perioperative complications (nonunion, postoperative infection, loss of fixation) and time to radiographic and clinical union. RESULTS: Forty-seven patients with 16 distal femur and 36 proximal tibia fractures were treated using temporary EF. Patients subsequently underwent ORIF (mean time from EF to ORIF = 5 days, range 1-23 days). Thirty-five fractures were open (Gustilo I = 8, II = 6, IIIA = 3, IIIB = 13, IIIC = 5) and 17 closed. Forty patients with 44 fractures reached 1-year follow-up. Of these, 36 patients with 40 (91%) fractures had healed both radiographically and clinically. The mean postoperative follow-up time was 14 months (range 3-68). Eight (16%) deep infections occurred, all in open fractures (Gustilo I = 2, IIIB = 3, IIIC = 3), with one patient requiring above knee amputation. Other complications included one hematoma, two malunions, one fixation failure, and one pin site infection. One patient died as a result of a stroke. CONCLUSIONS AND SIGNIFICANCE: Temporary bridging EF offers the advantage of early soft tissue and bone stabilization without the potential local risks of immediate ORIF in severely injured soft tissues, or the potential systemic risks in a severely traumatized patient. The 16% infection rate in this study, all occurring in open fractures, falls within the reported range for grade III open fractures (15%-20%). We conclude that the initial treatment of high-energy periarticular knee fractures with bridging EF, followed by planned conversion to internal fixation is a safe option in patients who are unsuitable for initial definitive surgery.

How accurately do novice surgeons place thoracic pedicle screws with the free hand technique?

STUDY DESIGN: Cadaver study. OBJECTIVE: To evaluate with direct observation the errors made when novice resident surgeons place thoracic pedicle screws. To determine how many specimens need to be instrumented to assure an improvement in accuracy to currently published levels. SUMMARY OF BACKGROUND DATA: Thoracic pedicle screw instrumentation has been shown to provide numerous benefits in spinal deformity surgery including 3 column fixation of the spinal elements, decreased need for thoracoplasty or anterior thoracic release and decreased operative time and blood loss. METHODS: Three orthopaedic residents inexperienced in pedicle screw placement received an introductory teaching session. Intact thoracic vertebral body specimens were harvested from 15 cadaver spines. Each vertebral body was mounted on a clear Plexiglas frame with only the posterior surface anatomy visible to the surgeon. Each resident surgeon instrumented 5 thoracic spines verbalizing all perceived pedicle wall violations as they occurred. An observer recorded the accuracy of the gearshift probe, flexible probe, tap, and screw placement. Critically perforated screws were defined as a greater than 2 mm breach of the pedicle wall. RESULTS: Two hundred ninety-seven pedicles in 149 intact vertebral body specimens were instrumented. Eighty-five (29%) screws were not fully within the pedicle. Sixty-three (74%) were noncritical violations and 22 (26%) were critical violations. There were 18 (21%) screw violations not perceived by the surgeon to be outside the pedicle. There was a decrease in the proportion of total screw violations by the third cadaver (P < 0.001) and in critical screw violations by the fourth cadaver (P = 0.01). CONCLUSION: Novice resident surgeons placing thoracic pedicle screws in cadavers were able to significantly improve by the fourth cadaver to accuracy levels documented in the literature. Surgeons in training shouldpractice these skills in the laboratory before proceeding to the operating room.

Role of PTEN and Akt in the regulation of growth and apoptosis in human osteoblastic cells.

Cancer cells are characterized by either an increased ability to proliferate or a diminished capacity to undergo programmed cell death. PTEN is instrumental in regulating the balance between growth and death in several cell types and has been described as a tumor suppressor. The chromosome arm on which PTEN is located is deleted in a subset of human osteosarcoma tumors. Therefore, we predicted that the loss of PTEN expression was contributing to increased Akt activation and the subsequent growth and survival of osteosarcoma tumor cells. Immunoblot analyses of several human osteosarcoma cell lines and normal osteoblasts revealed relatively abundant levels of PTEN. Furthermore, stimulation of cell growth or induction of apoptosis in osteosarcoma cells failed to affect PTEN expression or activity. Therefore, routine regulation of osteosarcoma cell growth and survival appears to be independent of changes in PTEN. Subsequently, the activation of a downstream target of PTEN activity, the survival factor Akt, was analyzed. Inappropriate activation of Akt could bypass the negative regulation by PTEN. Analyses of Akt expression in several osteosarcoma cell lines and normal osteoblasts revealed uniformly low basal levels of phosphorylated Akt. The levels of phosphorylated Akt did not increase following growth stimulation. In addition, osteosarcoma cell growth was unaffected by inhibitors of phosphatidylinositol-3 kinase, an upstream activator of the Akt signaling pathway. These data further suggest that the Akt pathway is not the predominant signaling cascade required for osteoblastic growth. However, inhibition of PTEN activity resulted in increased levels of Akt phosphorylation and enhanced cell proliferation. These data suggest that while abundant levels of PTEN normally maintain Akt in an inactive form in osteoblastic cells, the Akt signaling pathway is intact and functional.