Clinical features and radiological findings of 67 patients with SAPHO syndrome.

OBJECTIVES: The purpose of this study was to facilitate the understanding of the SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis) syndrome by analyzing the clinical and radiological features of 67 Japanese patients with SAPHO syndrome. METHODS: Sixty-seven Japanese patients (female/male: 44/23, mean age at onset: 48.5 years) were diagnosed with SAPHO syndrome from 2002 to 2013 at our hospital. Medical records and radiological imaging of these patients were retrospectively reviewed. RESULTS: Among the 67 patients, 41 had dermatological manifestations, such as palmoplantar pustulosis, acne, and psoriasis. Initial symptom was local pain in all patients, and the most common initial site of the symptom was the anterior chest. Bacterial and fungal cultures from 20 bone biopsies were all negative. Histopathological diagnosis of the specimens was non-specific inflammation in all cases. Bone lesions were observed in 65 patients (97.0%). On the other hand, articular lesions including enthesitis were found in 31 patients (46.2%). CONCLUSION: SAPHO syndrome had different clinical and radiological aspects. The clinical features were not remarkable, except the dermatological manifestations and the involvement of the anterior chest. Bone lesions including hyperostosis and osteitis were found radiographically in the majority of patients with SAPHO syndrome. These are the characteristics of the SAPHO syndrome, with the exclusion of other bone diseases.

Prediction of pathological fracture of the femoral shaft with an osteolytic lesion using a computed tomography-based nonlinear three-dimensional finite element method.

BACKGROUND: Physicians radiologically estimate the reduction in bone strength based on the size or location of bone tumors. The goal of this study was to clarify the relationship between the size or location of a bony defect and its mechanical strength using a computed tomography-based three-dimensional finite element method. METHODS: Computed tomography data of the right femur from two volunteers (one healthy male and one female patient with primary osteoporosis) were used for the present study. A spherical defect of various sizes and locations at the level of the isthmus of the femoral shaft was created on the three-dimensional finite element models to simulate the osteolytic bone tumor. We classified these defects into three types: inner erosion, cortical disruption, and outer erosion. Two types of mechanical testing were performed: axial compression and torsion. RESULTS: In the axial compression testing of the healthy male subject, the correlation coefficients between the defect rate and the failure load in the cortical disruption type, inner erosion type, and outer erosion type were -0.916, -0.358, and -0.106, respectively. In the torsion testing, they were -0.8744, -0.9001, and -0.8907, respectively. In the axial compression testing of the osteoporotic female subject, the correlation coefficients in the cortical disruption type, inner erosion type, and outer erosion type were -0.754, -0.621, and -0.158, respectively. In the torsion testing, they were -0.9199, -0.5098, and -0.8363, respectively. In both tests, the defect rate of the cortex increased and the bone strength decreased, especially in the cortical disruption type. CONCLUSION: The results of the present study demonstrate that osteolytic bone tumors can weaken the bone strength, particularly when perforation of the cortex occurs via tumor invasion. These results may be useful for risk assessment of pathological fractures due to primary and metastatic osteolytic bone tumors in clinical practice.

1α,25-dihydroxyvitamin D3 enhances fast-myosin heavy chain expression in differentiated C2C12 myoblasts.

We investigated the effect of VD3 (1α,25-dihydroxyvitamin D3) on the proliferating, differentiating and differentiated phases of C2C12 myoblasts, a mouse skeletal muscle cell line. VD3 treatment in 10% FBS (fetal bovine serum) inhibited the proliferation and viability of the cells in a dose-dependent manner. It also dose-dependently increased the percentage of cells in the G0/G1 phase as shown by flow cytometry. In the differentiating phase, VD3 treatment inhibited the formation of myotubes and the expression of total myosin heavy chain at both the mRNA and protein levels. In the differentiated phase, treatment had no significant effect on the amount of total myosin heavy chain, as Western blot analysis with MF20 antibody [DSHB (Developmental Studies Hybridoma Bank)] showed. However, significantly greater expression of fast myosin heavy chain in 1 nM VD3 was found by Western blot analysis with MY-32 (Sigma). Thus VD3 inhibited the proliferation of myoblasts during proliferating and differentiating phases, whereas it increased the expression of the fast myosin heavy chain isoform in the differentiated phase. The data indicate that an adequate concentration of VD3 might have an anabolic effect on differentiated skeletal muscle.

Tumors masked as frozen shoulders: a retrospective analysis.

BACKGROUND: It was reported that some shoulder tumors were misdiagnosed with frozen shoulder syndrome. The purposes of this study were to elucidate the incidence of the initial misdiagnosis with frozen shoulder syndrome among the patients with malignant shoulder tumors, and to clarify whether such initial misdiagnosis affected the time to make a final correct diagnosis or not. METHODS: Clinical records of 34 patients (age>40) with malignant shoulder tumors and those of 505 patients (age>40) with shoulder pain and stiffness were reviewed in the author's institute. The duration of the prediagnostic period was compared between the patients with and without an initial misdiagnosis as frozen shoulder syndrome. RESULTS: Among 34 tumor patients, 9 (26%) had been initially misdiagnosed with frozen shoulder syndrome. Two patients actually manifested shoulder pain and stiffness, although they did not have a record of misdiagnosis. Among 505 patients with shoulder pain and stiffness, 4 (0.8%) were diagnosed later as having malignant tumors. One of these 4 patients had been initially misdiagnosed with frozen shoulder syndrome. Consequently, 15 malignant tumors (10 bone tumors and 5 soft tissue sarcomas) were identified. Seven of them were intraosseous humeral tumors and 4 were localized in the scapular region, where patients themselves could not find them. In 10 patients, initial misdiagnosis as frozen shoulder syndrome did cause a significant delay to reach the correct diagnosis as malignant tumors (P=.035). CONCLUSION: Physicians should carefully re-examine the frozen shoulder patients with repeated plain radiographs followed by further imaging studies, if the conservative therapy fails.

Bladder perforation by orthopedic implants 26 years after limb-sparing surgery for left proximal femoral chondrosarcoma: A case report.

INTRODUCTION: The need for implant use during orthopedic surgeries has been increasing. Accordingly, increased implant failures have been reported. However, bladder perforation remains a rare complication after orthopedic surgery. Although a few reports have described bladder perforation after total hip arthroplasty, no previous studies have reported the migration of staples into the bladder after limb-sparing surgery. PRESENTATION OF CASE: A 65-year-old patient underwent limb-sparing surgery to remove a chondrosarcoma in the left proximal thigh. Twenty-six years after surgery, a staple that had been used to fix artificial ligaments to the pubis migrated to perforate the bladder, resulting in painful urination. The staple was removed, and her symptoms improved. DISCUSSION: In this case, bladder perforation by the staple resulted in painful urination. The bladder perforation was not detected until 26 years after the initial surgery. CONCLUSION: Our observations emphasize that implant complications may occur even after a long postoperative period, and the possibility of delayed bladder perforation from previous pelvic surgeries should be considered in patients presenting with urinary tract symptoms.

Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours.

AIMS: Fibroblast activation protein (FAP)/seprase and dipeptidylpeptidase-IV (DPP-IV)/CD26 are serine integral membrane proteases. They are involved in tissue remodelling, cancer invasion and metastases, mechanisms that are controversial. The aim was to identify cell types that express FAP and DPP-IV in human bone and soft tissue tumours, and to determine whether there are any correlations between the expression of FAP and DPP-IV and the malignant potential of tumours. METHODS AND RESULTS: This study analysed in situ expression in 25 malignant and 13 benign human bone and soft tissue tumours. Reverse transcriptase-polymerase chain reaction analyses confirmed mRNA expression of FAP and DPP-IV in all individuals. Immunohistochemistry using pre-fixed frozen sections revealed that FAP was positive in low-grade myofibroblastic sarcoma, the fibroblastic component of osteosarcomas, and malignant fibrous histiocytomas, but negative in Ewing's sarcomas and rhabdomyosarcomas. DPP-IV showed similar immunohistochemical results. Among benign tumours, non-ossifying fibromas, desmoid tumours and chondroblastomas expressed both FAP and DPP-IV. Giant cells expressed DPP-IV in giant cell tumours. CONCLUSIONS: Our data suggest that FAP and DPP-IV are consistently expressed in bone and soft tissue tumour cells that are histogenetically related to activated fibroblasts and/or myofibroblasts, irrespective of their malignancy. DPP-IV is also expressed in monocyte-macrophage lineage cells.

Sex steroid receptors expression and hormone-induced cell proliferation in human osteosarcoma.

Sex steroid receptors including estrogen receptors (ER), progesterone receptors (PR), and androgen receptors (AR) have been sporadically reported in human osteosarcoma or its cell lines. Therefore, sex steroids have been considered to play some roles in human osteosarcoma, but no systematic and detailed studies regarding the correlation between the status of these receptors in sarcoma cells and clinicopathological parameters have been reported. We examined the existence of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistry. We then characterized the potential influence of sex steroids on cell proliferation of osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed all of these receptors. ER-beta and PR were detected in the great majority of the cases (23 and 24 cases, respectively) but ER-alpha and aromatase were not detected in all the cases, and AR was detected only in eight cases. There was a significant positive correlation between ER-beta and Ki-67 (MIB1) labeling indexes. The absence of aromatase in tumors also suggests the relative importance of concentrations of circulating sex steroids. Proliferation of MG-63 cells was significantly stimulated by estradiol, progesterone, and 5 alpha-dihydrotestosterone (DHT), and was significantly suppressed by the addition of fulvestrant (ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR, respectively. Sex steroids, particularly estrogen and progesterone, are considered to play important roles in the regulation of cell proliferation in human osteosarcoma. In addition, these data suggest the potential for a novel endocrine therapy in osteosarcoma using clinically available inhibitors of progesterone and estrogen actions.

A patient with focal fibrocartilaginous dysplasia in the distal femur and review of the literature.

Focal fibrocartilaginous dysplasia (FFCD) is a rare and benign bone lesion that induces bowing deformity of the long bones in young children. Excessive production of fibrocartilage by abnormal differentiation in the metaphysis or by trauma during delivery or after birth is thought to cause growth disturbance. Radiologically, the lesion is characterized by a lucent defect with marginal sclerosis in the medial metaphysis of the long bone. However, there have been few reports about the initial radiological changes of FFCD before bowing started. We report a patient with FFCD in the left distal femur in whom the radiological changes were serially observed during the course of the disorder. A 2-week-old boy first visited our hospital because of left thigh pain. Plain radiographs did not show any abnormal findings at that time. At 10 weeks, a well-defined lucent defect with bony fragment inside was observed in the distal femoral medial cortex. At 1 year, this bony fragment gradually vanished but varus deformity progressed and reached approximately 40 degrees at the age of 2. After removal of the lesion, osteotomy and immobilization was performed with Ilizarov external fixator comprising rings, rods and wires. Complete bone union was achieved 3 months after operation. It is noteworthy that we could observe the initial radiological changes of FFCD before varus deformity occurred. As far as we know, there have been no descriptions of the bony fragment inside a lucent defect of the lesion. Radiological features may vary in the early phase of FFCD.

Osteofibrous dysplasia arising in the humerus: A case report.

Osteofibrous dysplasia is a benign fibro-osseous lesion of bone which is most commonly occurred in cortical bone of anterior mid-shaft of the tibia of infancy and childhood. This study reported a case of osteofibrous dysplasia arising in the humerus of adult, resulting in good prognosis after a surgical treatment. A 34-year-old male had felt left upper arm pain and was suspected as having a bone tumor at the humeral shaft by X-ray pictures. The tumor was suspected as the osteofibrous dysplasia of the humerus by a core needle biopsy. Intralesional curettage, intraoperative anhydrous ethanol therapy, and artificial bone graft were performed. Surgical specimens showed fibro-osseous lesion, which strongly indicated osteofibrous dysplasia. Seven years after the surgery, he has lived without any local recurrence and complaints. It is important to recognize that osteofibrous dysplasia can arise in the humerus of an older patient for appropriate diagnosis.

Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane.

Effects of aromatase inhibitors (AIs) on the human skeletal system due to systemic estrogen depletion are becoming clinically important due to their increasing use as an adjuvant therapy in postmenopausal women with breast cancer. However, possible effects of AIs on human bone cells have remained largely unknown. We therefore studied effects of AIs including the steroidal AI, exemestane (EXE), and non-steroidal AIs, Aromatase Inhibitor I (AI-I) and aminoglutethimide (AGM), on a human osteoblast. We employed a human osteoblast cell line, hFOB, which maintains relatively physiological status of estrogen and androgen pathways of human osteoblasts, i.e., expression of aromatase, androgen receptor (AR), and estrogen receptor (ER) beta. We also employed osteoblast-like cell lines, Saos-2 and MG-63 which expressed aromatase, AR, and ERalpha/beta in order to further evaluate the mechanisms of effects of AIs on osteoblasts. There was a significant increment in the number of the cells following 72 h treatment with EXE in hFOB and Saos-2 but not in MG-63, in which the level of AR mRNA was lower than that in hFOB and Saos-2. Alkaline phosphatase activity was also increased by EXE treatment in hFOB and Saos-2. Pretreatment with the AR blocker, flutamide, partially inhibited the effect of EXE. AI-I exerted no effects on osteoblast cell proliferation and AGM diminished the number of the cells. hFOB converted androstenedione into E2 and testosterone (TST). Both EXE and AI-I decreased E2 level and increased TST level. In a microarray analysis, gene profile patterns following treatment with EXE demonstrated similar patterns as with DHT but not with E2 treatment. The genes induced by EXE treatment were related to cell proliferation, differentiation which includes genes encoding cytoskeleton proteins. We also examined the expression levels of these genes using quantitative RT-PCR in hFOB and Saos-2 treated with EXE and DHT and with/without flutamide. HOXD11 gene known as bone morphogenesis factor and osteoblast growth-related genes were induced by EXE treatment as well as DHT treatment in both hFOB and Saos-2. These results indicated that the steroidal aromatase inhibitor, EXE, stimulated hFOB cell proliferation via both AR dependent and independent pathways.

Measurement of soft tissue elasticity in the congenital clubfoot using scanning acoustic microscope.

To compare the soft-tissue elasticity between the medial, lateral, and posterior aspects, the deltoid and calcaneofibular ligaments, and the medial, lateral, and posterior capsular tissues were collected from 27 feet of 16 congenital-clubfoot patients. The tissue sound speed, which closely correlates to the Young's modulus, was measured using a scanning acoustic microscope. Contrary to our expectations, lateral ligament showed a significantly higher sound speed than medial ligament (P=0.0023). Lateral capsule also showed a higher sound speed than the medial one (P=0.0338). The results of the study indicated that the lateral soft tissues including the ligaments and capsule underwent severe contracture in congenital clubfoot.

Chondrosarcoma of the distal phalanx of the great toe.

Enchondromas are the most common benign cartilaginous bone tumors of the toe. In contrast, chondrosarcomas are very uncommon in the foot. We report an unusual case of a chondrosarcoma arising in the great toe. The patient was a 62-year-old woman whose chief complaint was swelling of her left great toe. Radiography showed subtle punctate calcification and mild sclerosis and irregularity of the distal phalanx in the great toe. Magnetic resonance imaging showed extraskeletal growth. The distal phalanx was amputated. Histologic examination demonstrated a grade 1 chondrosarcoma. Two years after surgery, the patient was free of recurrence and lung metastasis.

SAPHO syndrome with a tumour-like bony proliferative lesion in distal femur. A case report.

SAPHO syndrome is a group of bone and joint abnormalities associated with skin lesions. A 29-year-old male presented with severe acne on his trunk and anterior chest wall, right knee and foot pain. Radiographs and magnetic resonance images showed hyperostosis in the sternocostoclavicular region, sclerosis of one-third of the right distal 5th metatarsal bone and bony outgrowth from the medial condyle of the right femur. The histological findings of the biopsy specimen were consistent with-those of old osteomyelitis. All fungal and microbacterial cultures were negative. Pain and swelling of the right knee and foot repeated remission and aggravation. There were no radiological changes of the above-mentioned lesions noted within 4-years follow-up.

Ollier's disease treated with grafting using alpha-tricalcium phosphate cement. A case report.

Ollier's disease is a rare disorder characterized by multiple enchondromas with a unilateral predominance, especially in fingers in early childhood. We experienced a case of Ollier's disease treated four times with simple curettage from the age of 2 years and alpha-tricalcium phosphate cement grafting at the age of 21 years. The forth curettage was performed when the patient was 15 years old and preoperative X-rays had shown remarkable finger deformities. Postoperative casting of the involved joints was necessary to prevent fractures but led to some finger contractures. Following X-rays demonstrated incredible improvement of the appearance. This suggests that simple curettage alone at an early stage of Ollier's disease provide cosmetic improvement. At the age of 21 years our patient showed enlargement of the intramedullary finger lesions again. Some lesions seemed to be impending pathological fractures. This time we chose alpha-tricalcium phosphate cement to fill the cavities after curettage had been carried out. Harvesting a large amount of autologous bone was not required. All activities of daily life could be resumed immediately after surgery and none of the finger joints showed further restriction of motion. X-rays taken three years after the operation showed new bone ingrowth surrounding the material with little evidence of absorption. To our knowledge, this may be the first case of Ollier's disease treated with artificial bone grafting reported in the English literature.

Ankle dislocation without accompanying malleolar fracture. A case report.

Dislocation of the tibiotalar joint without associated fracture is rare. We present here a 21-year-old man who sustained open posteromedial dislocation of the left ankle without malleolar facture when he jumped and sprained his right ankle while playing basketball. The most likely mechanism is forced flexion applied to the ankle joint leading to a rupture of the anterior capsule and lateral structures of the ankle followed by an accelerating inversion stress leading to a posteromedial dislocation of the talus from the tibial condyle. Transient paresthesia was noted in the area of the superficial peroneal nerve. At surgery, the anterior part of the tibiotalar joint capsule and anterior talofibular ligament were detached from their original sites. The calcaneofibular ligament was also detached with its associated periosteum and a tiny avulsed bony fragment. The articular facets of the tibia and talus were intact. The treatment consisted of wound irrigation, debridement, reduction and capsular suture followed by immobilization with a short leg cast. About 10 degrees of loss in the range of dorsiflexion was observed. The patient achieved good long-term functional results.

Heterotopic ossification of the distal portion of biceps femoris: case report and review of the literature.

Heterotopic ossification is the formation of mature lamellar bone in soft tissue. We report a very unusual case of heterotopic ossification arising in the distal portion of the biceps femoris muscle. A 29-year-old woman presented with knee pain after playing golf. She had had no apparent history of trauma. Radiography of the knee showed a calcified mass adjacent to the lateral side of her knee joint. The radiological diagnosis was calcification of the lateral collateral ligament. The pain soon disappeared without treatment. At the age of 45 years, she complained of a growing mass in her left knee that was occasionally painful. Computed tomography and magnetic resonance imaging demonstrated a well matured ossified mass in the lateral side of her left knee. Radiologically and macroscopically, it was found to be in continuity with the distal part of biceps femoris. The mass was excised en bloc. Microscopically, the lesion was mainly composed of well-matured lamellar bone with bone marrow and islands of cartilage showing enchondral ossification. No apparent zoning was found. Cellular atypia was not observed. Extraskeletal osteosarcoma was ruled out. The mass was diagnosed as a heterotopic ossification arising from the distal part of biceps femoris.

Gene expression analysis of ectopic bone formation induced by electroporatic gene transfer of BMP4.

Implantation of bone morphogenetic protein (BMP) using a carrier or by BMP gene transfer into rodent muscle can induce bone formation. Implanted BMP becomes bioactive immediately after implantation. In BMP gene transfer, there is a time-lag between the secretion of gene products and bone formation. We analyzed the gene expression of chondrogenic and osteogenic specific markers in the process of ectopic bone formation by using semi-quantitative RT-PCR. A plasmid vector containing mouse BMP4 gene (pCAGGS-BMP4) was transferred into the gastrocnemius muscles of mice using electroporation. Histological examination revealed the process of endochondral bone formation in the pCAGGS-BMP4 transferred muscles. As chondrogenic markers, aggrecan gene maximal expression was detected on day 7 and decreased by day 14, and for collagen X the gene maximal expression was on day 10. As osteogenic markers, osteocalcin (OCN), bone sialoprotein (BSP) and osteopontin (OPN) gene expressions were clearly detected from day 10 and then increased by day 14. In conclusion, the present study proved that ectopic bone formation by BMP4 gene transfer into the muscle induced endochondral ossification that corresponded well with that to that by implantation of demineralized bone matrix.

Osteolipoma arising adjacent to the sternoclavicular joint. A case report.

A 45-year-old woman presented with one-year history of a mass on her chest. Computed tomography and magnetic resonance imaging demonstrated a tumour near the sternoclavicular joint. The tumour was diagnosed as osteolipoma histologically after resection. Osteolipoma is a rare tumour and this may be the first report of osteolipoma arising adjacent to the sternoclavicular joint.