Risk factors for vertebral fractures and bone loss after denosumab discontinuation: A real-world observational study.

BACKGROUND: Denosumab discontinuation without subsequent bisphosphonates (BPs) is associated with bone loss and multiple vertebral fractures. OBJECTIVE: Identifying risk factors for bone loss and vertebral fractures after denosumab discontinuation. METHODS: This retrospective study measured the outcome of 219 women with osteoporosis who discontinued denosumab treatment and received subsequent treatment with zoledronate, other BPs or a selective estrogen receptor modulator (SERM), or no therapy. Fracture rate, longitudinal bone mineral density (BMD) changes and bone turnover markers (BTMs) within 2 years after denosumab discontinuation were analysed. Linear regression analysis evaluated loss of BMD and age, BMI (kg/m2), denosumab treatment duration, pre-treatment, prior fracture state, baseline T-scores, use of glucocorticoids or aromatase inhibitors and BMD gains under denosumab therapy. RESULTS: 171 women received zoledronate after denosumab discontinuation, 26 had no subsequent treatment and 22 received other therapies (other BPs or a SERM). Zoledronate was associated with the fewest vertebral fractures (hazard ratio 0.16, p = 0.02) and all subsequent therapies retained BMD at all sites to some extent. Higher BMD loss was associated with younger age, lower BMI, longer denosumab treatment, lack of prior antiresorptive treatment and BMD gain under denosumab treatment. BTM levels correlated with denosumab treatment duration and bone loss at the total hip, but not the lumbar spine. CONCLUSIONS: Compared to no subsequent therapy, zoledronate was associated with fewer vertebral fractures after denosumab. Further, BMD loss depended on denosumab treatment duration, age, prior BP therapy and BMD gain under denosumab therapy, whereas BTM levels were associated with bone loss at the total hip and denosumab treatment duration.

Atlas-based knee osteophyte assessment with ultrasonography and radiography: relationship to arthroscopic degeneration of articular cartilage.

OBJECTIVES: To investigate intra- and inter-reader agreement of ultrasonography (US) and conventional radiography (CR) for the evaluation of osteophyte presence and size within the tibiofemoral joint. In addition, to correlate these findings with arthroscopic degeneration of the articular cartilage. METHOD: Forty adult patients with knee pain were enrolled in this study. Knee CR and US scanning of the medial and lateral bone margins were performed on all patients. A novel atlas for the US grading of knee osteophytes was used in the evaluation. The number and size of the osteophytes were evaluated semi-quantitatively in two rounds from both the CR images (four readers) and the US images (14 readers). The Noyes grading system was used for the evaluation of arthroscopic degeneration of the articular cartilage in 26 patients. RESULTS: On average, intra- and inter-reader US and CR agreement was substantial and comparable to each other (κ = 0.60-0.72). US detected more osteophytes than CR at both the medial (65% vs. 48%) and lateral (70% vs. 60%) compartments. A statistically significant correlation between CR- or US-based osteophyte and arthroscopy grades was observed only for US at the medial compartment (rs = 0.747, p < 0.001). CONCLUSIONS: The detection of knee osteophytes using the novel US atlas is as reproducible as reading conventional radiographs. US is more sensitive to detect knee osteophytes than CR. Furthermore, osteophytes detected with US correlate significantly with arthroscopic cartilage changes at the medial knee compartment whereas those detected by CR do not.

[Musculoskeletal ultrasound I - «pearls and crystals¼]. / Ultraschall am Bewegungsapparat I - «Perlen und Kristalle¼

This article reviews the applications of high resolution ultrasound (HRUS) which were discussed at the SGUM congress in Davos in the talk «pearls and crystals¼. Sonography is an excellent and validated tool in the diagnostics and assessment e.g. of spondylo-arthritis and crystal deposition diseases. Enthesitis is a typical feature of SpA. The Sensitivity of HRUS diagnosing enthesitis is higher compared to the clinical examination. High frequency US probes allow furthermore an accurate assessment in crystal deposition diseases. Sonography is able to detect various typical pathologies in gout, pseudogout and apatite deposition disease. Will HRUS in the near future be able to replace microscopy in the diagnostics of crystal deposition diseases?

[Musculoskeletal ultrasound II - «why are bats better than physicians¼]. / Ultraschall am Bewegungsapparat II oder - wieso Fledermäuse Besser sind als Ärzte.

This article reviews the aspects which were discussed at the SGUM congress in Davos in the talk «why are bats better than physicians¼. The talk focussed on modern aspects of Ultrasound (US) diagnostics at the locomotor system. High frequency US probes allow accurate diagnosis, initial assessment and follow up in Rheumatoid Arthritis and Osteo-Arthritis. Basic pathologic features in these pathologic conditions in form of synovitis, erosion and cartilage damage are described. In case of entrapment neuropathies - first of all in carpal tunnel syndrome - pathognomonic sonomorphologic changes can be detected and allow to confirm a clinical suspicion. The correct indication for diagnostic or therapeutic interventions at the musculoskeletal system can be critically verified and if necessary revised. The guidance of the intervention by US guarantees high accuracy of needle placement and thereby increases the diagnostic yield and the therapeutic success of injections/infiltrations.

[Musculoskeletal puncture, injection and infiltration: swiss rheumatologists' point of view]. / Muskuloskelettale Punktion, Injektion und Infiltration: Standpunkt von Schweizer Rheumatologen.

Arthrocentesis, injection and infiltration of joints and soft tissues belong to the basic procedures in rheumatology. The indications and the practical performance are based on experience and tradition. Nowadays, a crucial reappraisal and adaption of indications and technical aspects appear important in the light of new evidence and technical developments. The main indications for puncture remain the search of an infectious arthritis and reduction of intra-articular pressure due to effusion. Good indications for the injection of glucocorticoids are inflammation in sterile joints and activated osteoarthritis. The local infiltration with corticosteroids in mechanically induced enthesopathies at the lateral epicondyle of the humerus or at the plantar fascia have to be questioned in the light of recent publications which show that this common practice is associated with a poorer outcome than without injection.

[Ultrasound and arthritis]. / Ultraschall und Arthritis.

Musculoskeletal ultrasonography (US) is an established and validated imaging technique in rheumatology. Ultrasonography is able to directly visualize soft tissue pathologies such as synovial tissue changes. Pathological findings in superficial cartilage, bone lesions and synovial tissue changes in the context of rheumatoid arthritis, spondyloarthritis or crystal arthropathies may only be seen by sonography or detected earlier by ultrasonography compared to conventional imaging techniques. The activity of an inflammatory arthropathy can be visualized using Doppler and power Doppler US. US is helpful in the detection of early inflammatory changes, particularly in patients with undifferentiated arthritis and/or unremarkable conventional radiography. In addition to diagnosis in early arthritis and monitoring of therapy in rheumatoid arthritis, sonography is able to detect pivotal pathologies in spondyloarthritis and crystal deposition diseases such as gout, pseudogout and apatite deposition disease. Ultrasound-guided diagnostic and therapeutic interventions are characterized by their excellent accuracy and improvement of clinical effectiveness compared to unguided procedures. In conclusion, ultrasonography plays a pivotal role in the assessment and monitoring of therapy in rheumatic diseases.

A randomised controlled trial of spinal manipulative therapy in acute low back pain.

OBJECTIVE: To determine whether treatment with spinal manipulative therapy (SMT) administered in addition to standard care is associated with clinically relevant early reductions in pain and analgesic consumption. METHODS: 104 patients with acute low back pain were randomly assigned to SMT in addition to standard care (n = 52) or standard care alone (n = 52). Standard care consisted of general advice and paracetamol, diclofenac or dihydrocodeine as required. Other analgesic drugs or non-pharmacological treatments were not allowed. Primary outcomes were pain intensity assessed on the 11-point box scale (BS-11) and analgesic use based on diclofenac equivalence doses during days 1-14. An extended follow-up was performed at 6 months. RESULTS: Pain reductions were similar in experimental and control groups, with the lower limit of the 95% CI excluding a relevant benefit of SMT (difference 0.5 on the BS-11, 95% CI -0.2 to 1.2, p = 0.13). Analgesic consumptions were also similar (difference -18 mg diclofenac equivalents, 95% CI -43 mg to 7 mg, p = 0.17), with small initial differences diminishing over time. There were no differences between groups in any of the secondary outcomes and stratified analyses provided no evidence for potential benefits of SMT in specific patient groups. The extended follow-up showed similar patterns. CONCLUSIONS: SMT is unlikely to result in relevant early pain reduction in patients with acute low back pain.

Assessing the intra- and inter-reader reliability of dynamic ultrasound images in power Doppler ultrasonography.

OBJECTIVE: To assess the intra-reader and inter-reader reliabilities of interpreting ultrasonography by several experts using video clips. METHOD: 99 video clips of healthy and rheumatic joints were recorded and delivered to 17 physician sonographers in two rounds. The intra-reader and inter-reader reliabilities of interpreting the ultrasound results were calculated using a dichotomous system (normal/abnormal) and a graded semiquantitative scoring system. RESULTS: The video reading method worked well. 70% of the readers could classify at least 70% of the cases correctly as normal or abnormal. The distribution of readers answering correctly was wide. The most difficult joints to assess were the elbow, wrist, metacarpophalangeal (MCP) and knee joints. The intra-reader and inter-reader agreements on interpreting dynamic ultrasound images as normal or abnormal, as well as detecting and scoring a Doppler signal were moderate to good (kappa = 0.52-0.82). CONCLUSIONS: Dynamic image assessment (video clips) can be used as an alternative method in ultrasonography reliability studies. The intra-reader and inter-reader reliabilities of ultrasonography in dynamic image reading are acceptable, but more definitions and training are needed to improve sonographic reproducibility.

Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR "Train the trainers" course.

OBJECTIVE: To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging "gold standard". METHODS: The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. RESULTS: Taking an agreement in US examination of 10 out of 14 experts into account, the overall kappa for all examined joints was 0.76. Calculations for each joint region showed high kappa values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). kappa Values for bone lesions, bursitis, and tendon tears were high (kappa = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). CONCLUSION: Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US.

[Nocardia cyriacigeorgici: First report of invasive human infection]. / Nocardia cyriacigeorgici: Erstbeschreibung als invasive Infektion.

BACKGROUND: Diagnostic laboratories increasingly offer bacterial identification to the species level. The 17 nocardia species known to date differ in their clinical presentation, antibiotic resistance patterns and geographic distribution. The discovery of a new species with pathogenicity for humans calls for the characterization of its clinical and epidemiological properties. PATIENTS AND METHODS: Nocardia isolated from multifocal brain abscesses of an immunocompromised patient were further identified by the analysis of their cellular fatty acids and sequencing of the 16S ribosomal DNA. Quantitative antibiotic resistance testing was performed with E-tests. RESULTS: The 16S ribosomal DNA analysis showed a 99 % homology to Nocardia cyriacigeorgici. This is the first report of this species as an invasive human pathogen. N. cyriacigeorgici was found susceptible for meropenem, amikacin, ceftriaxon and cotrimoxazole. The combination of surgical drainage and antibiotic treatment for 13 months was curative. CONCLUSIONS: N. cyriacigeorgici has the potential to cause invasive infections at least in immunocompromised patients. Comparing clinical and in vitro characteristics with N. asteroides, the main causative agent of nocardial infections in Europe, we found no clinically relevant differences.

[Ultrasound diagnosis of the locomotor system]. / Ultraschalldiagnostik am Bewegungsapparat.

Improvements of ultrasound technology with knew equipments allowed enormous advances in all fields of medicine during the last years. Several conditions concerning technical equipment and training of the operator have to be fulfilled to guarantee sufficient quality of the diagnostic information obtained in musculoskeletal ultrasound, Ultrasound is most commonly used in the assessment of soft tissue disease, detection of fluid collection, but can also be used to visualise structures such as cartilage and bone surfaces. Bone surface changes like erosions may be seen before they are apparent on plain x ray or even magnetic resonance imaging. Dynamic assessment of joint and tendon movements allows better understanding of the functional disorders than mainly static imaging methods. Advantages of ultrasound include its non-invasiveness, portability, relative inexpensiveness, lack of ionising radiation, and its ability to be repeated as often as necessary, making it particularly useful in the monitoring of treatment. Guidance of diagnostic aspiration, biopsy and injection treatment improves quality and security of these interventions. Newer ultrasound techniques including colour and power Doppler imaging, as well as bubble contrast agents and three dimensional reconstructions are promising tools for the future.

Cardiovascular, endocrine and renal effects of atrial natriuretic peptide in essential hypertension.

Plasma concentrations of human atrial natriuretic peptide (hANP) and effects of synthetic alpha-hANP on blood pressure (BP), on endocrine and metabolic variables, and on renal function were investigated in 10 patients with essential hypertension. Alpha-human atrial natriuretic peptide was given intravenously as a 50-micrograms bolus followed by a 45-min infusion at 0.1 microgram/kg per min. The following effects were observed: (1) a marked rise in plasma alpha-hANP, (2) a progressive fall in BP (from 181/127 to 165/109 mmHg) and plasma volume, (3) a probably baroreflex-mediated sympathetic activation, evidenced by raised heart rate and plasma norepinephrine levels, (4) an increase in serum free fatty acids and circulating insulin (+45%), (5) an enhanced diuresis (+770%) and excretion of sodium (+665%), chloride (+524%), phosphate (+518%), other electrolytes, amino acids and free water clearance, (6) biphasic responses in the glomerular filtration rate (GFR) and p-aminohippurate (PAH) clearance, with initial increases (+40 and 30%, respectively) followed by a rapid return to (GFR), or even a fall below (PAH clearance) control values, and (7) a marked rise in the filtration fraction. Plasma antidiuretic hormone and urinary prostaglandin E2, F2 alpha and dopamine levels were not modified during alpha-hANP infusion, while plasma renin increased. Discontinuation of alpha-hANP was followed by rises in plasma aldosterone, the aldosterone:renin ratio and cortisol. Compared with previously studied normal subjects, in the hypertensive patients alpha-hANP caused a distinctly greater diuresis and electrolyte excretion but lowered BP only slightly more. In essential hypertension, as in normal man, alpha-hANP circulates in the blood and may exert a wide spectrum of cardiovascular, metabolic, endocrine and renal actions.