Rebound-associated vertebral fractures after discontinuation of denosumab for the treatment of maxillitis.

We reported a 69-year-old female who discontinued denosumab due to dental treatment and subsequently suffered rebound-associated vertebral fractures 10 months after the last injection. This case raised an alarm regarding the discontinuation of denosumab for dental treatment. Denosumab, a human monoclonal antibody administered by subcutaneous injection, to the best of our knowledge, is the only fully investigated inhibitor of receptor activator of nuclear factor kappa B ligand. Discontinuation of denosumab leads to bone turnover rebound and rapid bone mineral density loss. Several studies have reported rebound-associated vertebral fractures after discontinuation of denosumab. We report on a new case of rebound-associated vertebral fractures after discontinuation of denosumab. A 69-year-old female, who withdrew from denosumab treatment after 3 years due to maxillitis, presented to our hospital with severe low back pain without any history of trauma. Ten months had passed since the last injection. Magnetic resonance imaging showed five acute vertebral fractures, which appeared to be rebound-associated vertebral fractures caused by discontinuation of denosumab due to dental treatment. This case clearly demonstrates the risk of discontinuation of denosumab for dental treatment.

A retrospective analysis of nonresponse to daily teriparatide treatment.

UNLABELLED: Some patients with osteoporosis do not respond to teriparatide treatment. Prior bisphosphonate use, lower bone turnover marker (BTMs) concentrations, and lower early increases in BTMs were significantly associated with a blunted lumbar spine (LS) bone mineral density (BMD) response to daily treatment with teriparatide, although the impact was limited. INTRODUCTION: Some osteoporosis patients do not respond to teriparatide treatment. To better understand the factors underlying treatment nonresponses, we compared nonresponders' and responders' characteristics. METHODS: We retrospectively analyzed 354 male and female patients with osteoporosis who were administered teriparatide (20 µg/day) for 24 months. The patients were categorized as responders (≥3 % lumber spine (LS) bone mineral density (BMD) increase) or nonresponders (<3 % LS BMD increase), and the groups were compared. RESULTS: The univariate analyses determined that prior bisphosphonate use, a lower baseline procollagen type I N-terminal propeptide (PINP) concentration and a lower urinary N-telopeptide of type I collagen (uNTX) concentration at baseline were significantly associated with teriparatide nonresponses, but these factors were not significant following multivariate analysis. Diminished early increases in the bone turnover markers (BTMs) were also related to nonresponses after teriparatide treatment began. In the nonresponders, the mean (standard deviation (SD)) absolute LS and femoral neck (FN) BMD changes were -0.002 g/cm(2) (0.032) and -0.010 g/cm(2) (0.045), respectively. In the responders, the mean (SD) absolute LS and FN BMD changes were 0.118 g/cm(2) (0.056) and 0.021 g/cm(2) (0.046), respectively. The serum PINP and uNTX levels increased rapidly in both groups, but the responders showed higher early absolute serum PINP and uNTX increases. CONCLUSIONS: The factors associated with nonresponses were prior bisphosphonate use, lower baseline BTM levels, and lower early increases in the BTMs after starting teriparatide treatment, but the impact of these factors on achieving a ≥3 % LS BMD increase at 24 months was limited.

Usefulness of daily teriparatide treatment in elderly patients over 80 years of age.

UNLABELLED: The percent and absolute lumbar spine and femoral neck bone mineral densities and procollagen type I N-terminal propeptide (PINP) and urinary N-telopeptide level increases noted after teriparatide 20 µg/day treatment for 24 months were similar in the older (age ≥ 80 years) and younger (age < 80 years) subgroups. INTRODUCTION: Many individuals are living into their eighth and ninth decades, but little is known about the efficacy of osteoporosis medication for this population. We retrospectively compared usefulness of daily teriparatide therapy in osteoporosis patients ≥80 and <80 years to detect possible age-related differences. METHODS: We analyzed 628 osteoporosis patients treated with teriparatide 20 µg/day for 24 months. The primary efficacy measures were changes in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) over 24 months. Changes in serum procollagen type I N-terminal propeptide levels and urinary N-telopeptide (uNTX) excretion were also measured. Patients were divided into age subgroups (older, ≥80 years; younger, <80 years) for BMD and bone turnover marker comparison. RESULTS: In the older subgroup, the percent LS BMD significantly increased by 14.6 ± 10.4 % (mean ± SD) and FN BMD significantly increased by 4.5 ± 10.7 % at 24 months. In the younger subgroup, the percent LS BMD significantly increased by 12.2 ± 8.5 % and FN BMD significantly increased by 2.9 ± 8.3 % at 24 months. In the older subgroup, the mean absolute LS BMD change was 0.111 ± 0.071 g/cm(2) and FN BMD change was 0.019 ± 0.043 g/cm(2). In the younger subgroup, the mean absolute LS BMD change was 0.098 ± 0.065 g/cm(2) and FN BMD change was 0.016 ± 0.045 g/cm(2). The percent and absolute BMD increases in LS and FN and changes in PINP and uNTX were similar between the subgroups. CONCLUSIONS: The usefulness of daily teriparatide treatment is not age dependent.

Analysis of daily teriparatide treatment for osteoporosis in men.

UNLABELLED: The percent and absolute lumbar spine and femoral neck bone mineral densities and absolute procollagen type I N-terminal propeptide (PINP) increases following a 20-µg/day teriparatide treatment for 12 months were similar in men and women regardless of sex differences. INTRODUCTION: Several placebo-controlled studies have measured the effects of daily teriparatide in men and postmenopausal women with osteoporosis but none have directly compared the effects between these groups. We retrospectively compared the effects of daily teriparatide therapy in men and postmenopausal women with osteoporosis and investigated biochemical markers of bone turnover to detect possible sex differences. METHODS: Patients (563; 75 men and 488 women) with osteoporosis were retrospectively investigated. All patients were administered with teriparatide at 20 µg/day for 12 months. The primary efficacy measure was changed in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) after 12 months of treatment. The change in serum levels of procollagen type I N-terminal propeptide (PINP) and urinary N-telopeptide (uNTX) excretion after 4, 8 and 12 months of treatment were also measured. RESULTS: In men, the percent LS BMD significantly increased by 11.3 ± 9.9 % (mean ± standard deviation (SD)) and the FN BMD increased by 0.4 ± 6.4 % without a significant difference at 12 months. In postmenopausal women, the percent LS BMD significantly increased by 9.6 ± 8.1 % and the FN BMD significantly increased by 2.4 ± 7.8 % at 12 months. The percent and absolute BMD increases in LS and FN between men and women were similar. The absolute increases in PINP were similar in both groups at 4, 8 and 12 months. However, the absolute increases in uNTX were significantly lower in men than in women at 8 and 12 months. CONCLUSION: Daily teriparatide treatment was as effective in men as in postmenopausal women regardless of sex differences.

An algorithm using the early changes in PINP to predict the future BMD response for patients treated with daily teriparatide.

UNLABELLED: About two thirds of patients with a procollagen type I N-terminal propeptide (PINP) increase of >80 µg/l at 1 month after starting teriparatide therapy showed a ≥10 % increase in lumbar spine (LS) bone mineral density (BMD) from baseline at 12 months. We recommend this algorithm as an aid in the clinical management of patients treated with daily teriparatide. INTRODUCTION: An algorithm using PINP is provided in osteoporotic patients with teriparatide treatment. The correlations between the early changes in PINP and the subsequent BMD changes after daily teriparatide therapy were studied to develop an algorithm to monitor patients. METHODS: We evaluated whether early changes in PINP correlated with the changes in BMD at 12 months and developed an algorithm using the early changes in PINP to predict the upcoming BMD increases. RESULTS: The highest correlation coefficient for the relationship between PINP and LS BMD response was determined for the absolute change in PINP at 1 month and the percent change in LS BMD at 12 months (r = 0.36, p <0.01). Using a receiver operator curve analysis, we determined that an 80 µg/l increase in PINP was the most convenient predictor of a 10% increase in LS BMD from baseline (area under curve = 0.72). Using a cut-off value of 80 µg/l, the positive predictive value for predicting a 10% increase in LS BMD from baseline to 12 months was 65%. CONCLUSION: Greater short-term changes in PINP with teriparatide therapy are associated with greater 12-month increases in LS BMD. About two thirds of patients with a PINP increase of >80 µg/l at 1 month after starting treatment showed a ≥10 % increase in LS BMD from baseline at 12 months. We recommend this algorithm as an aid in the clinical management of patients treated with teriparatide.

Efficacy of the dynamic radiographs for diagnosing acute osteoporotic vertebral fractures.

UNLABELLED: We investigated the efficacy of dynamic radiographs for diagnosing acute osteoporotic vertebral fractures (OVFs) compared with supine radiographs or sitting radiographs alone. Evaluation of the dynamic radiographs was superior to the other evaluations. Dynamic radiographs provide a convenient and useful method of diagnosing acute OVFs. INTRODUCTION: Identifying acute OVFs on plain radiographs is difficult. We studied a new approach to identify acute OVFs on the basis of fracture mobility. METHODS: We performed a retrospective radiographic analysis of 472 acute OVFs (<3 weeks after onset), which were diagnosed on the basis of magnetic resonance imaging of T5 through L5 (a total of 5,239 vertebrae). Supine lateral radiographs were compared with sitting lateral radiographs to determine the presence or absence of mobility. Vertebrae showing changes in the vertebral body height were diagnosed as acute OVFs. We analyzed the diagnostic accuracy on the basis of comparative supine and sitting lateral radiographs and compared it with that of radiographs obtained in the supine or the sitting position alone. RESULTS: Of the 472 acute OVFs diagnosed, 313 (66 %) exhibited vertebral mobility on supine lateral and sitting lateral radiographs. Correct diagnoses of acute OVFs or no acute OVFs were made in 4,883 vertebrae. There were 159 unreadable OVFs (3 %), and 197 previous OVFs (4 %) were misdiagnosed as acute OVFs. The sensitivity was 66 % and the specificity was 96 %. Evaluation of the mobility of acute OVFs in the supine and the sitting position was superior to evaluation using radiographs in either the supine or the sitting position alone. CONCLUSIONS: Dynamic radiographs provide a convenient way to identify acute OVFs.

Deep-vein thrombosis after resection of musculoskeletal tumours of the lower limb.

The aim of this study was to define the incidence of venous thromboembolism (VTE) and risk factors for the development of deep-vein thrombosis (DVT) after the resection of a musculoskeletal tumour. A total of 94 patients who underwent resection of a musculoskeletal tumour between January 2003 and December 2005 were prospectively studied. There were 42 men and 52 women with a mean age of 54.4 years (18 to 86). All patients wore intermittent pneumatic compression devices and graduated compression stockings. Ultrasound examination of the lower limbs was conducted to screen for DVT between the fifth and ninth post-operative days. DVT was detected in 21 patients (22%). Of these, two were symptomatic (2%). One patient (1%) had a fatal pulmonary embolism. Patients aged ≥ 70 years had an increased risk of DVT (p = 0.004). The overall incidence of DVT (both symptomatic and asymptomatic) after resection of a musculoskeletal tumour with mechanical prophylaxis was high. It seems that both mechanical and anticoagulant prophylaxis is needed to prevent VTE in patients who have undergone the resection of a musculoskeletal tumour.

The influence of fondaparinux on the diagnosis of postoperative deep vein thrombosis by soluble fibrin and D-dimer.

INTRODUCTION: There are many reports concerning the fondaparinux prophylaxis of deep vein thrombosis (DVT) after surgery, but little is known about the usefulness of diagnosing DVT by the thrombotic markers such as soluble fibrin (SF) and D-dimer in patients treated with fondaparinux. The main purpose of this study was to evaluate the accuracy of SF and D-dimer tests for DVT screening in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) treated with fondaparinux. MATERIALS AND METHODS: A total of 519 patients who underwent THA or TKA were evaluated. SF and D-dimer levels were evaluated on postoperative days 1, 4, 7, 14 and 21. DVT was confirmed by ultrasonography 4 days after surgery. RESULTS: The incidence of DVT in patients treated with fondaparinux was significantly lower than in patients without fondaparinux. The SF test on postoperative day 1, and the D-dimer test on postoperative days 1, 4, and 7 were useful in untreated patients. However, in the patients treated with fondaparinux, the D-dimer test on postoperative day 7 only was useful for DVT screening. CONCLUSION: The accuracy of SF and D-dimer test for the diagnosis of DVT was decreased by administration of fondaparinux. A new strategy for diagnosing DVT might be required for patients receiving fondaparinux.

Diffuse gliomas in an adolescent with multiple enchondromatosis (Ollier's disease).

Ollier's disease is characterized by the hamartomatous proliferation of cartilage cells, producing masses termed chondromas. A patient presented with Ollier's disease which was found to be associated with diffuse gliomas. Investigating this disease is crucial as there is a high risk of sarcomatous transformation of the skeletal lesions as well as an increased risk of developing extra-osseous malignancies.

Differentiation between neurofibromas and malignant peripheral nerve sheath tumors in neurofibromatosis 1 evaluated by MRI.

PURPOSE: The imaging discrimination between neurofibroma (NF) and malignant peripheral nerve sheath tumor (MPNST) is clinically very important. The purpose of this study is to define the criteria for the differential diagnosis between NF and MPNST on MRI in neurofibromatosis 1 (NF1). METHODS: A total of 37 patients with NF1, 18 NFs and 19 MPNSTs were evaluated by MRI at 1.5 T. Magnetic resonance imaging (MRI) findings were compared using univariate and multivariate analyses. RESULTS: The MRI findings characteristic of MPNST (p < 0.05) were an irregular tumor shape (15/19 in MPNST vs. 5/18 in NF), unclear margin (13/19 in MPNST vs. 6/18 in NF), intra-tumoral lobulation (12/19 in MPNST vs. 3/18 in NF), presence of high signal-intensity area on T1-weighted images (T1WI) (12/19 in MPNST vs. 1/18 in NF), no target sign (0/19 in MPNST vs. 12/18 in NF), inhomogeneous enhancement on contract-enhanced T1WI (17/18 in MPNST vs. 9/16 in NF) and a lower rate of enhanced area (54% in MPNST vs. 87% in NF) were critical indicators to differentiate MPNST from NF. A multivariate analysis showed that intra-tumoral lobulation and the presence of a high signal-intensity area on T1WI were considered to be diagnostic indicators of MPNST. The sensitivity and specificity for these two items were 63.2, 83.3, 63.2 and 87.5%, respectively. CONCLUSION: MRI shows features which were helpful for differentiating MPNST from NF.

Changes in bone mineral density in transient osteoporosis of the hip.

Transient osteoporosis of the hip is a disorder characterised by pain, and associated with temporary osteopaenia. Although osteopaenia is the essence of the condition, data do not exist about the local bone density of the femoral neck if no medication is administered. We describe three patients who were treated with limitation of weight-bearing only. Repeated bone mineral density measurements were obtained, and that at the femoral neck was lowest two months after the onset of the condition. The mean reduction in bone mineral density when compared with an age-matched control group was 13% (3% to 24%). Spontaneous recovery was observed in all patients.

Soft-tissue sarcoma mimicking large haematoma: a report of two cases and review of the literature.

We report on 2 patients with soft-tissue sarcomas mimicking large haematomas. Neither patient had a medical history of trauma or bleeding tendency. In a patient with a large leiomyosarcoma in the buttock, insufficient biopsy material from initial surgeries precluded a correct diagnosis. In the second patient with epithelioid sarcoma of the forearm, fasciotomy was repeatedly performed for compartment syndrome arising from the tumour. It is important to reconfirm prior trauma and investigate the clinical course and images of patients with an unusual history of haematoma in the extremities. The possibility of a malignant tumour should be suspected, and repeated biopsies should be performed if necessary.

Suppression of tumor necrosis factor-alpha by beta2-adrenoceptor activation: role of mitogen-activated protein kinases in renal mesangial cells.

OBJECTIVE: The present study examined the inhibitory effect of beta2-adrenoceptor activation on the mitogen-activated protein kinase (MAPK) cascades and the contribution of these pathways to the suppression of tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS)-stimulated rat renal mesangial cells. MATERIALS AND METHODS: Experiments were performed using cultured mesangial cells in the presence of LPS (1 microg/ml) and/or the beta2-adrenoceptor agonist, terbutaline (10(-6) 10(-8) M). The levels of extracellular signal-regulated kinase-1 and 2(Erk 1/2), p38, c-Jun N-terminal protein kinase (JNK) and TNF-alpha were estimated. RESULTS: LPS activated Erk-1/2 and p38 levels, by 4.7-fold and 1.8-fold, respectively (P < 0.05), which were suppressed by terbutaline (10(-6) - 10(-8) M) in a dose dependent way. These inhibitory actions of terbutaline were prevented by the beta2-adrenoceptor antagonist, ICI 118,551(10(-6) M) but not by an inhibitor of the cAMP-PKA pathway, H-89 (5 x 10(-6) M). The selective MAPK/Erk-1 inhibitor, PD98059 (10(-5) M) and the specific p38 inhibitor SB203580 (10(-5) M) significantly decreased LPS-induced TNF-alpha production in the cells. CONCLUSIONS: Inhibition of MAPK cascades (Erkl/2 and p38) plays an important role in the suppression of TNF-alpha following beta2-adrenoceptor activation but the inhibitory effect on MAPK is independent of the cAMP-PKA pathway in the mesangial cell.

Role of ultrasonography in the detection of intraductal spread of breast cancer: correlation with pathologic findings, mammography and MR imaging.

The purpose of this study was to assess the role of US in the detection of intraductal spread of breast cancer in comparison with mammography (MMG) and MRI. In 46 patients with breast cancer, US features of the intraductal component were classified as ductal type or distorted type. Histopathologically, 29 of 46 (63%) cases had intraductal components, and the sensitivity, specificity, and accuracy rates in detection of intraductal spread were 89, 76, and 85%, respectively. Each US pattern demonstrated good correspondence to the histologic components, and the distorted type correlated well with comedo-type carcinoma. Mammography was performed in all cases, and the sensitivity, specificity, and accuracy rates in detection of intraductal spread were 55, 100, and 72%, respectively. In comedo type, MMG could diagnose the extent of intraductal spread more accurately compared with US examination. Magnetic resonance imaging comparison was available in 25 cases. Magnetic resonance imaging depicted intraductal extension as an enhanced area during the early phase of a contrast enhancement study with a sensitivity of 93%. Ultrasound and MRI were closely related in terms of morphologic characteristics: the ductal type of US image correlated well with linear enhancement on MRI, whereas the distorted type correlated with regional or segmental enhancement. Current US examination is useful in depicting the intraductal spread of breast cancer; however, US has a tendency to underestimate intraductal component of comedo type compared with MMG and MRI.

Chemoprevention of biliary carcinogenesis in syrian hamsters by the novel carboxamide derivative IS-741 after initiation with N-nitrosobis(2-oxopropyl)amine (BOP).

To elucidate the possible inhibitory effect of a novel carboxamide derivative (IS-741) on biliary carcinogenesis, Syrian hamsters were subjected to cholecystoduodenostomy and ligation of the distal end of the common duct, and then given a regular diet (group I) or a diet containing 200 p.p.m. of IS-741 (group II). All hamsters were subcutaneously injected with N-nitrosobis(2-oxopropyl)amine until 10 weeks after surgery, and continued to feed on their respective dietary regimen until termination of the experiment at 16 weeks after surgery. Biliary adenocarcinomas were evaluated histologically. Non-cancerous and cancerous hepatobiliary tract tissues were analyzed for phospholipase A(2) (PLA(2)) activity, myeloperoxidase (MPO) activity, and the concentrations of prostaglandin (PG), i.e., prostaglandin E(2), 6-ketoprostaglandin F(1)alpha and thromboxane B(2). IS-741 significantly inhibited the development and multiplicity of hepatobiliary adenocarcinomas and reduced the proliferating cell nuclear antigen labeling indices in non-cancerous hepatobiliary tissues, compared with group I. The anti-cancerous effect of IS-741 was associated with a significant inhibition of PLA(2) and MPO levels in non-cancerous tissues of the extrahepatic biliary tract and the liver, and in cancerous tissue of the liver. Furthermore, IS-741 reduced the production of PGs in non-cancerous hepatobiliary tissues, compared with group I. Although the precise mechanism of action of IS-741 in preventing biliary tumorigenesis remains to be elucidated, it is likely to be related to modulation of arachidonic acid metabolism and/or suppression of neutrophil accumulation.

An experimental teleradiology transmission system using a high-speed ATM backbone network.

We evaluated the performance of an experimental teleradiology system based on a high-speed ATM backbone network. Image acquisition, transmission and the disk-to-display processing times were measured. Computerized tomography (CT) scans printed on 14 inch x 17 inch (36 cm x 43 cm) films were digitized and transferred over the network. The average time for the entire process was 1 min 30 s. Three radiologists interpreted 20 cases. For CT image interpretation, the reading time for one case ranged from 2 to 12 min (mean 6 min 46 s) on a monitor, and from 1 to 3 min (mean 1 min 31 s) with the original film. The ATM backbone network operating at 156 Mbit/s provided sufficient speed for remote consultation. However, further improvements in the operability of the system, especially the image viewing station, are necessary before it will be satisfactory for clinical use.

Analysis of poly(ethyl methacrylate)s by on-line hyphenation of liquid chromatography at the critical adsorption point and nuclear magnetic resonance spectroscopy

Liquid chromatography at the critical adsorption point (LC CAP) with on-line NMR detection (on-line LC CAP NMR) was utilized for analysis of tacticity distribution of stereo-regular poly(ethyl methacrylate)s (PEMAs). The separation of a model PEMA sample composed of four constituents with similar molar masses (Mw = (14-16) x 10(3) g mol-1) differing in their tacticity (rr triad content = 0, 33, 68, and 89%) was achieved by LC CAP with a mixed eluent composed of acetone, acetone-d6, and cyclohexane. The tacticity composition within each peak eluted from the LC CAP column was directly determined by a 750-MHz 1H NMR spectrometer that was used as a real-time detector in the continuous-flow mode. Tacticity distribution in a particular PEMA sample with mm/mr/rr = 2/45/53 and narrow molar mass distribution of Mw/Mn = 1.05 has been revealed by the LC CAP NMR technique.

Eye-tracking device comparisons of three methods of magnetic resonance image series displays.

This study evaluated the effectiveness of three kinds of display methods for magnetic resonance (MR) image interpretation using an eye-tracking device. Seven radiologists interpreted head MR studies by using a single monitor (17-inch, 1,024 X 1,280 bit) in the 4 images/screen display format. Three paging modes were compared: (A) rapid paging only, (B) multiple image series display at the same slice position with consecutive rapid paging, and (C) simultaneous display of multiple series with each image series being browsed independently. Using an eye-mark camera, the radiologist's point of fixation and the duration of fixation were recorded during actual image interpretation. In mode A, the duration of fixation was short, and the points of fixation were distributed randomly over the visual field. In mode B, the points of fixation were clustered chiefly on a specific image series. In mode C, the points of fixation were not clustered on a specified series, but the duration of viewing the T2 series was relatively long. The total tracing area in mode B and C was smaller than that in mode A. Multiple series display, in which selected key series of slices could be viewed effectively, was found to be suitable for MR image interpretation.