Insulin-like growth factor-I is required to maintain muscle volume in adult mice.

Insulin-like growth factor-I (IGF-I) is a peptide with diverse functions, among them regulation of embryonic development and bone homeostasis. Serum IGF-I levels decline in the elderly; however, IGF-I function in adults has not been clearly defined. Here, we show that IGF-I is required to maintain muscle mass in adults. We crossed Igf-I flox'd and Mx1 Cre mice to yield Mx1 Cre/Igf-Iflox/flox (IGF-I cKO) mice, and deleted Igf-I in adult mice by polyIpolyC injection. We demonstrate that, although serum IGF-I levels significantly decreased after polyIpolyC injection relative to (Igf-Iflox/flox) controls, serum glucose levels were unchanged. However, muscle mass decreased significantly after IGF-I down-regulation, while bone mass remained the same. In IGF-I cKO muscle, expression of anabolic factors such as Eif4e and p70S6K significantly decreased, while expression of catabolic factors MuRF1 and Atrogin-1 was normal and down-regulated, respectively, suggesting that observed muscle mass reduction was due to perturbed muscle metabolism. Our data demonstrate a specific role for IGF-I in maintaining muscle homeostasis in adults.

Tumor necrosis factor receptor-associated factor 6 is required to inhibit foreign body giant cell formation and activate osteoclasts under inflammatory and infectious conditions.

Osteoclasts and foreign body giant cells (FBGCs) are derived from common progenitors and share properties such as multi-nucleation capacity induced by cell-cell fusion; however, mechanisms underlying lineage determination between these cells remain unclear. Here we show that, under inflammatory conditions, osteoclasts are stimulated in a manner similar to M1 macrophages, while formation of FBGCs, which exhibit M2-like phenotypes, is inhibited in a manner similar to that seen in M1/M2 macrophage polarization. FBGC/osteoclast polarization was inhibited by conditional knockout of tumor necrosis factor receptor associated factor 6 (Traf6) in adults in vivo and in vitro. Traf6-null mice were previously reported to die soon after birth, but we found that Traf6 deletion in adults did not cause lethality but rather inhibited osteoclast activation and prevented FBGC inhibition under inflammatory conditions. Accordingly, basal osteoclastogenesis was significantly inhibited by Traf6 deletion in vivo and in vitro and accompanied by increased bone mass. Lipopolysaccharide-induced osteoclast formation and osteolysis were significantly inhibited in Traf6 conditional knockout mice. Our results suggest that Traf6 plays a crucial role in regulating M1 osteoclast and M2 FBGC polarization and is a potential therapeutic target in blocking FBGC inhibition, antagonizing osteolysis in inflammatory conditions, and increasing bone mass without adverse effects in adults.

Pelvic Tilt Displacement Before and After Artificial Hip Joint Replacement Surgery.

BACKGROUND: Prediction of pelvic displacement before total hip arthroplasty (THA) is important for accurate acetabular implant placement. This study aimed to evaluate the effect of contralateral joint conditions on pelvic displacement after THA. METHODS: A total of 355 cases that underwent computed tomography before and after THA for osteoarthritis due to developmental dysplasia were assessed. The pelvic plane was based on preoperative and postoperative day 1 computed tomography images. The displacement in the anteversion direction was expressed as +. Subjects with a minimal joint space <2 mm in the contralateral hip joint were in group N; subjects with ≥2 mm were in group W; subjects with THA were in group P; and subjects who underwent THA simultaneously on both sides were in group B. The Bartlett test was used when conducting the equal variance test among the groups. The F test was used for pairwise comparison. A P value <.01 was considered statistically significant. RESULTS: Groups N, W, P, and B had 49, 227, 55, and 24 cases, respectively, and their displacements were -0.2° ± 2.7°, 0.8° ± 3.9°, 0.5° ± 2.6°, and 1.1° ± 4.0°, respectively; the variance between the groups was significantly different (P = .0001). The differences between groups W and N (P = .0020), between groups W and P (P = .0003), and between groups P and B (P = .0086) were statistically significant. CONCLUSION: When the contralateral joint space is wide, the variance of the displacement is high. The contralateral joint affects pelvic displacement.

Clinical results of the conserve plus metal on metal hip resurfacing: an independent series.

The purpose of the present study was to report the clinical and radiographic results of an independent series of the Conserve Plus hip resurfacing. Five hundred forty-eight consecutive hip resurfacings were performed using the Conserve Plus prosthesis in 458 patients (350 males) with a mean age of 48.3 years (range 19 to 66). No patients were lost to follow-up. At a mean follow-up of 6.6 years (3.9 to 11.9) thirty (5.4%) hips required conversion to a total hip arthroplasty (THA) (20 males, 10 females, mean age=48.3±7.3 years). Five-year survival with as revision endpoint was 94.5% (95% CI: 93.5% to 95.5%). This study confirms the good clinical results previously reported with the Conserve Plus hip resurfacing device.

Do revised hip resurfacing arthroplasties lead to outcomes comparable to those of primary and revised total hip arthroplasties?

BACKGROUND: A theoretical clinical advantage of hip resurfacing (HR) is the preservation of femoral bone. HR femoral component revision reportedly yields postoperative function comparable to that of primary THA. However, few studies have looked at the outcome of both HR femoral and acetabular side revisions. QUESTIONS/PURPOSES: We determined whether (1) patients undergoing HR revision to THA have perioperative measures and outcome scores comparable to those of patients undergoing primary THA or revision of primary THA and (2) patients undergoing HR revision of both components have perioperative measures and outcome scores comparable to those of patients undergoing HR revision of the femoral component only. METHODS: We retrospectively reviewed and compared 22 patients undergoing revision HR to a THA to a matched (age, sex, BMI) group of 23 patients undergoing primary THA and 12 patients undergoing primary THA revision. Patients completed the WOMAC and SF-12 questionnaires before surgery and at latest followup (range, 24-84 months for HR revision, 28-48 months for primary THA, and 24-48 months for revision THA). Blood loss, days in hospital, complications, and outcome scores were compared among groups. RESULTS: We observed no differences in SF-12 scores but observed lower WOMAC stiffness, function, and total scores in the HR revision group than in the primary THA group. Patients undergoing HR revision of both components had comparable SF-12 and WOMAC stiffness, function, and total scores but overall lower WOMAC pain scores compared to patients undergoing HR revision of the femoral side only. The HR revision group had greater intraoperative blood loss compared to the primary THA group but not the revision THA group. CONCLUSIONS: The perioperative measures and outcome scores of HR revision are comparable to those of revision THA but not primary THA. Longer followup is required to determine whether these differences persist. Patients undergoing HR revision of one or both components can expect comparable stiffness and function. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

A Case of Fragility Fracture of the Pelvis Initially Diagnosed as Osteoarthritis of the Hip.

We present the case of a 58-year-old woman who presented with anterior groin pain, initially diagnosed with hip osteoarthritis (OA), scheduled for total hip arthroplasty, and subsequently diagnosed with an occult fragility fracture of the pelvis (FFP) by preoperative computed tomography (CT) examination. We diagnosed the patient with pre-existing hip OA and a bilateral sacrum and left pubic tubercle fracture that exacerbated the groin pain. We operated on the FFP followed by simultaneous bilateral total hip arthroplasty. Given the high prevalence of hip OA and the increasing incidence of FFP, comorbidity of these 2 entities should be ruled out. Even if hip OA is apparent, plain radiographs are insufficient to rule out FFP, necessitating a thorough clinical examination, followed by a CT examination if an FFP is suspected.

Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis.

Bone homeostasis requires a delicate balance between the activities of bone-resorbing osteoclasts and bone-forming osteoblasts. Various molecules coordinate osteoclast function with that of osteoblasts; however, molecules that mediate osteoclast-osteoblast interactions by simultaneous signal transduction in both cell types have not yet been identified. Here we show that osteoclasts express the NFATc1 target gene Efnb2 (encoding ephrinB2), while osteoblasts express the receptor EphB4, along with other ephrin-Eph family members. Using gain- and loss-of-function experiments, we demonstrate that reverse signaling through ephrinB2 into osteoclast precursors suppresses osteoclast differentiation by inhibiting the osteoclastogenic c-Fos-NFATc1 cascade. In addition, forward signaling through EphB4 into osteoblasts enhances osteogenic differentiation, and overexpression of EphB4 in osteoblasts increases bone mass in transgenic mice. These data demonstrate that ephrin-Eph bidirectional signaling links two major molecular mechanisms for cell differentiation--one in osteoclasts and the other in osteoblasts--thereby maintaining bone homeostasis.

Short-Term Outcomes of Total Hip Arthroplasty after Liver Transplantation.

BACKGROUND: Idiopathic osteonecrosis of the femoral head (ONFH) frequently occurs after liver transplantation (LT) because of lifelong administration of corticosteroids or immunosuppressants and often requires total hip arthroplasty (THA). This study examines patient characteristics and short-term outcomes of THA after LT. METHODS: We observed 9 hips in 7 patients who underwent THA from August 2015 to December 2017 for ONFH after LT (group L). Cementless implants were inserted in all hips. Medical records were retrospectively reviewed to reveal reasons for LT, type of donor, and period from LT to THA. Preoperative laboratory data, operative time, intraoperative blood loss, complication rates, and Harris Hip Score were compared with a control group of 27 cementless THAs in 27 patients with ONFH. RESULTS: Causative diseases were liver cirrhosis (n = 4), type B fulminant hepatitis (n = 1), congenital biliary atresia (n = 1), and iatrogenic biliary tract injury (n = 1). Four livers were from living donors and 3 from cadavers. Mean time from LT to THA was 10.4 (1-20) years. Preoperative blood test showed a significant decrease in platelet count (178 vs 268 [∗103/µl]) and rise in total bilirubin (1.1 vs 0.7 [mg/dL]) in group L. There was no significant difference in operative time (86 vs 100 [minutes]), but intraoperative blood loss (303 vs 163 [mL]) increased significantly in group L. There were no significant differences in complication incidence or Harris Hip Score between the 2 groups. CONCLUSION: THA after LT requires caution because risks for bleeding increase. However, short-term outcomes appear to be equivalent to normal THA.

Curved periacetabular osteotomy via a novel intermuscular approach between the sartorius and iliac muscles.

INTRODUCTION: Herein, we describe and evaluate a curved periacetabular osteotomy (CPO) via an intermuscular approach (IM-CPO) between the sartorius and iliac muscles. METHODS: Between January 2009 and January 2016, IM-CPO was performed in 17 joints (16 patients), and a traditional CPO was performed in 17 joints. The length of incision at wound closure, operative time, intraoperative blood loss, serum creatinine kinase (CK) level the day after surgery, correctional angle, walking ability assessed using the gait items of the Harris Hip Score (at 3 and 6 months after surgery), and perioperative complications were evaluated. Group differences were assessed using t-tests. RESULTS: The IM-CPO and CPO groups did not differ in the mean operative time (130 minutes and 124 minutes, respectively), mean serum CK the day after surgery (349 IU/L and 425 IU/L, respectively), or mean correctional angle (24.9° and 24.6°, respectively). The mean incision length was significantly shorter in the IM-CPO group (8.3 cm) compared to that in the CPO group (9.5 cm). The mean walking ability was significantly higher in the IM-CPO group (24.2 points) compared to that in the CPO group (20.9 points) at 3 months after surgery, but not at 6 months after surgery (26.4 points and 24.9 points, respectively). No serious complications were observed in either group. CONCLUSION: In addition to demonstrating a similarly satisfactory correctional angle, IM-CPO is anticipated to enable early weight-bearing and recovery of walking ability. Thus, IM-CPO is considered a superior surgical technique.

Pronounced femur malunion after pathological bone fracture due to a simple bone cyst in the shaft of the femur, treated using Ilizarov fixation: a case report.

BACKGROUND: Although a simple bone cyst carries the risk of pathological fractures, it rarely causes severe deformity. Here we report a case of severe femoral deformity after multiple pathological fractures due to simple bone cysts, and consider the reason for the progression of malunion despite multiple previous treatments. Finally, we propose a treatment option for malunion correction. CASE PRESENTATION: A 9-year, 7-month-old Japanese girl was referred to our facility with obvious deformity of her right femur, caused by multiple simple bone cyst-related pathological fractures. The deformity included bowing of approximately 90° and an internal rotation of 60° in the middle third of the femoral shaft. To correct this deformity, we excised the lesion, thus shortening the femur, then corrected the alignment and applied an Ilizarov fixator to extend the bone. At present, 3 years after surgery, the deformity has not recurred and our patient is living without any limitations in daily activities or regular exercise. CONCLUSIONS: When a long bone is in a prolonged state of deformation, the deformity not only progresses as the bone grows, but the soft tissues remain unbalanced and treatment becomes increasingly difficult. To prevent increasing bone deformity and fragility, the deformity should be corrected as quickly as possible using intramedullary nailing or other fixation techniques. We believe that our shortening-distraction method is effective for the treatment of severe deformity with unbalanced soft tissues.

Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1.

UNLABELLED: Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression of bone matrix proteins. We found that expression of Thbs1 and Thbs2 was reduced in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1-/-Thbs2-/- mice share an edge-to-edge bite. Therefore, reduced expression of thrombospondins may contribute to craniofacial dysmorphism independently of osteosclerosis. INTRODUCTION: Tg mice overexpressing Fra1, a component of the transcription factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell autonomous abnormalities in osteoblasts. The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts. MATERIALS AND METHODS: In osteoblastogenic cultures, altered bone matrix production by Fra1 overexpression was monitored using Alizarin red staining, quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was examined by bone histomorphometry. Craniofacial parameters were measured on radiographs and using CT. RESULTS: Thrombospondin-1 (Thbs1) and thrombospondin-2 (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg mice, as well as Thbs1-/- Thbs2-/- mice, which do not show osteosclerosis, exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism. CONCLUSIONS: These data suggest that reduced expression of thrombospondins in Fra1 Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis.

Pseudoarthrosis of the ilium after periacetabular osteotomy that was treated by cemented total hip arthroplasty: a case report.

BACKGROUND: Preserving the hip joint to delay arthroplasty for patients with acetabular dysplasia-associated early-stage osteoarthritis has become more common, and several surgical procedures have demonstrated pain relief and improved hip joint function. Periacetabular osteotomy, one of the joint-preserving surgical procedures of the hip, provides favorable outcomes, although there are no reports of total hip arthroplasty being used to treat pseudoarthrosis of the periacetabular osteotomy segment. Therefore, we report a case of pseudoarthrosis in the osteotomy segment after periacetabular osteotomy. The patient was treated using modified total hip arthroplasty and achieved a favorable short-term outcome. CASE PRESENTATION: A 62-year-old Japanese woman was diagnosed with bilateral acetabular dysplasia at the age of 50 years, and underwent right and left periacetabular osteotomy at the ages of 52 and 55 years, respectively. When she was 61-years old, she experienced repeated episodes of left coxalgia during walking, with increasing pain at rest, and subsequently visited our department. Plain radiography and computed tomography of her left hip joint confirmed pseudoarthrosis of the periacetabular osteotomy segment. In addition, narrowing of her left hip joint space was observed, which indicated advanced osteoarthritis of the hip. Therefore, she underwent left total hip arthroplasty when she was 62-years old. During the surgery, fibrous fusion of the periacetabular osteotomy segment was confirmed via fluoroscopy, although no abnormal mobility was observed. Thus, the osteotomy segment was fixed with one absorbable screw and two bone pegs (which were prepared using allogeneic bone), and the acetabular cup was fixed using cement. Her postoperative course was generally favorable and bone fusion of the periacetabular osteotomy segment was confirmed at 3 years and 6 months after surgery. Her modified Harris hip score was 43 before the surgery and had improved to 90 at the final follow-up. CONCLUSIONS: Modified total hip arthroplasty was successfully used to treat osteoarthritis of the hip and pseudoarthrosis of the periacetabular osteotomy segment. This procedure achieved pseudoarthrosis region bone fusion and a favorable postoperative outcome.

Acetabular labral tear complicating idiopathic osteonecrosis of the femoral head treated by labral repair with hip arthroscopy: a case report.

INTRODUCTION: It has been well documented that labral tear is frequently associated with femoroacetabular impingement and dysplasia of the hip; however, there have been few reported cases of labral tear associated with idiopathic osteonecrosis of the hip. Here we report the case of a patient with labral tear associated with idiopathic osteonecrosis of the femoral head who was treated by hip arthroscopy, with a favorable short-term outcome. CASE PRESENTATION: Under the diagnosis of systemic lupus erythematosus, a 28-year-old Japanese woman was treated with the oral administration of steroid in 2007. A year after the treatment, she developed right hip joint pain and was diagnosed with idiopathic osteonecrosis of the femoral head at our institution. In November of 2011, she revisited our hospital when her right hip joint pain exacerbated and she became unable to walk. On the visit, the anterior impingement sign and Patrick test were positive. Radiography and magnetic resonance imaging in 2011 demonstrated neither spreading of the osteonecrosis area nor collapse of the femoral head in the right joint; however, magnetic resonance imaging showed a high-intensity area in the articular labrum in a T2-weighted image, leading to a diagnosis of labral tear. She underwent labral repair with hip arthroscopy in August of 2012. Now, 1 year after surgery, she does not feel any pain during walking and her modified Harris hip score has improved from 20 prior to surgery to 85. CONCLUSION: The case indicated that it is important to be aware of the possibility of labral tear in patients with idiopathic osteonecrosis of the femoral head, when spreading of the osteonecrosis area or collapse of the femoral head has not been seen on magnetic resonance imaging.

Sciatic palsy after total hip arthroplasty associated with vascular graft occlusion.

Sciatic nerve palsy is a well-recognised complication of total hip arthroplasty, and causes include direct injury during surgery (crushing or electrocautery), compression or stretching of the nerve, thermal damage caused by leaked bone cement, trauma during dislocation or reduction of the hip, haematoma, traction caused by leg lengthening or inadvertent intraneural injection from nerve blocks. We describe what we believe to be a case of sciatic nerve ischemia due to intra-operative arterial occlusion, and we discuss the vascular anatomy which may have contributed.