Marcy B. Bolster

Imaging of in vitro and in vivo bones and joints with continuous-wave diffuse optical tomography.

WWe present what is believed to be the first absorption and scattering images of in vitro and in vivo bones and joints from continuous-wave tomographic measurements. Human finger and chicken bones embedded in cylindrical scattering media were imaged at multiple transverse planes with Clemson multi-channel diffuse optical imager. Both absorption and scattering images were obtained using our nonlinear, finite element based reconstruction algorithm. This study shows that diffuse optical tomography (DOT) has the potential to be used for detection and monitoring of bone and joint diseases such as osteoporosis and arthritis.

Three-dimensional diffuse optical tomography of bones and joints

We present for the first time full three-dimensional (3D) volumetric reconstruction of absorption images of in vitro and in vivo bones and joints from near-infrared tomographic measurements. Imaging experiments were conducted on human finger and chicken bones embedded in cylindrical scattering media using a Clemson multichannel diffuse optical imager. The volumetric optical images were recovered with our 3D finite element based reconstruction algorithm. Our results show that 3D imaging methods can provide details of the joint structure/composition that would be impossible from two-dimensional imaging methods.

Scleroderma lung study (SLS): differences in the presentation and course of patients with limited versus diffuse systemic sclerosis

Objectives: Pulmonary fibrosis is a leading cause of death in systemic sclerosis (SSc). This report examines the differences at baseline and over 12 months between patients with limited versus diffuse cutaneous SSc who participated in the Scleroderma Lung Study. Methods: SSc patients (64 limited; 94 diffuse) exhibiting dyspnoea on exertion, restrictive pulmonary function and evidence of alveolitis on bronchoalveolar lavage and/or high-resolution computed tomography (HRCT) were randomised to receive cyclophosphamide (CYC) or placebo and serially evaluated over 12 months. Results: Baseline measures of alveolitis, dyspnoea and pulmonary function were similar in limited and diffuse SSc. However, differences were noted with respect to HRCT-scored fibrosis (worse in limited SSc), and to functional activity, quality of life, skin and musculoskeletal manifestations (worse in diffuse SSc) (p<0.05). When adjusted for the baseline level of fibrosis, both groups responded similarly to CYC with regard to lung function and dyspnoea (p<0.05). Cyclophosphamide was also associated with more improvement in skin score in the diffuse disease group more than in the limited disease group (p<0.05). Conclusions: After adjusting for the severity of fibrosis at baseline, CYC slowed the decline of lung volumes and improved dyspnoea equally in the limited and the diffuse SSc groups. On the other hand, diffuse SSc patients responded better than limited patients with respect to improvements in skin thickening.

Survival and predictors of mortality in systemic sclerosis-associated pulmonary arterial hypertension: outcomes from the pulmonary hypertension assessment and recognition of outcomes in scleroderma registry.

To assess cumulative survival rates and identify independent predictors of mortality in patients with incident systemic sclerosis (SSc)–associated pulmonary arterial hypertension (PAH) who had undergone routine screening for PAH at SSc centers in the US.

Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry

Background Patients with normal (mean pulmonary arterial pressure (mPAP) ≤20 mm Hg) and borderline mean pulmonary pressures (21–24 mm Hg) are “at risk” of developing pulmonary hypertension (PH). The objectives of this analysis were to examine the baseline characteristics in systemic sclerosis (SSc) with normal and borderline mPAP and to explore long-term outcomes in SSc patients with borderline mPAP versus normal haemodynamics. Methods PHAROS is a multicentre prospective longitudinal cohort of patients with SSc “at risk” or recently diagnosed with resting PH on right heart catheterisation (RHC). Baseline clinical characteristics, pulmonary function tests, high-resolution CT, 2-dimensional echocardiogram and RHC results were analysed in normal and borderline mPAP groups. Results 206 patients underwent RHC (results showed 35 normal, 28 borderline mPAP, 143 resting PH). There were no differences in the baseline demographics. Patients in the borderline mPAP group were more likely to have restrictive lung disease (67% vs 30%), fibrosis on high-resolution CT and a higher estimated right ventricular systolic pressure on echocardiogram (46.3 vs 36.2 mm Hg; p<0.05) than patients with normal haemodynamics. RHC revealed higher pulmonary vascular resistance and more elevated mPAP on exercise (≥30; 88% vs 56%) in the borderline mPAP group (p<0.05 for both). Patients were followed for a mean of 25.7 months and 24 patients had a repeat RHC during this period. During follow-up, 55% of the borderline mPAP group and 32% of the normal group developed resting PH (p=NS). Conclusions Patients with borderline mPAP have a greater prevalence of abnormal lung physiology, pulmonary fibrosis and the presence of exercise mPAP ≥30 mm Hg.

SCLERODERMA AND RELATED CONDITIONS

Systemic sclerosis is a generalized disorder characterized by fibrosis and microvascular injury in affected organs. Despite being recognized nearly 250 years ago, knowledge regarding pathogenesis remains limited, and treatment remains directed at symptomatic improvement. Early recognition of systemic sclerosis, however, is important in order to monitor for specific disease complications (i.e., fibrosing alveolitis, scleroderma renal crisis) as well as initiate manifestation specific therapies that improve quality of life.

Assessment and management of scleroderma lung disease.

Lung disease is a major cause of morbidity and is the leading cause of mortality in patients with systemic sclerosis, most commonly occurring as interstitial lung disease or as pulmonary hypertension. Cyclophosphamide has been used to treat the interstitial lung disease and a placebo-controlled trial is planned. Potent pulmonary vasodilators, many of which have been studied in primary pulmonary hypertension, are now undergoing study in patients with systemic sclerosis.

Bisphosphonate use is associated with reduced risk of myocardial infarction in patients with rheumatoid arthritis

Bisphosphonates have been shown to reduce mortality in patients with osteoporotic fractures, but the mechanism is unclear. Bisphosphonates have immunomodulatory effects that may influence the development of vascular disease. We sought to determine if bisphosphonate use is associated with a reduced risk of myocardial infarction (MI) in a rheumatoid arthritis (RA) population with high prevalence of bisphosphonate use and vascular disease. Adult patients with RA enrolled in the National Data Bank for Rheumatic Diseases, a longitudinal study of RA patients enrolled continuously from U.S. rheumatology practices between 2003 and 2011, were included in the analysis (n = 19,281). Patients completed questionnaires every 6 months. including questions on medication use, demographic information, clinical information, and health status. MIs were confirmed by a central adjudicator. Among the 5689 patients who were treated with bisphosphonates at some time during the study period, the risk of MI while on bisphosphonate compared to when not on bisphosphonate was 0.56 (95% confidence interval [CI], 0.37–0.86; p < 0.01) after adjustment for multiple confounders. In models including all 19,281 treated and untreated patients, the adjusted risk of first MI was 0.72 (95% CI, 0.54–0.96; p = 0.02) and of all MIs it was 0.72 (95% CI, 0.53–0.97; p = 0.03) in bisphosphonate users compared to nonusers. This finding suggests a potential mechanism for the mortality reduction observed with bisphosphonate medications.

Current approaches to osteoporosis treatment.

Purpose of reviewOsteoporosis is a skeletal disorder in which bone strength is decreased leading to an increased risk of fracture. In line with advances in knowledge of bone biology, the past several years have held major therapeutic advances in osteoporosis treatment. In this article, we review the current approaches to osteoporosis treatment with a focus on issues of interest to the practicing rheumatologist. Recent findingsIn addition to the bisphosphonates, the introduction of denosumab, teriparatide and selective oestrogen-receptor modulators, as well as the development of new therapeutic agents (romosozumab and odanacatib) has opened the door to new approaches, including individualization of treatment in different clinical circumstances based on patient comorbidities and preference; combination therapy to optimize treatment effect; and consideration of goal-based treatment. Postmarketing surveillance of bisphosphonates has revealed several safety concerns including osteonecrosis of the jaw and atypical femoral fractures. Bisphosphonate drug holidays should be considered in patients on bisphosphonate therapy because prolonged treatment may be associated with adverse events. SummarySubstantial progress has been made in the past several years in the understanding and modification of osteoporosis management. Many conditions encountered by rheumatologists are associated with bone loss; therefore, the rheumatologist needs to be aware of the current approaches in osteoporosis management.

Consternation and questions about two vertebroplasty trials.

Should we abandon this popular procedure? Or are there considerations that may mitigate the negative findings of these two trials?