Risk factors predicting the 'time to first fracture' and its association with imminent fractures: a substudy of the FRISBEE cohort.

Only previous glucocorticoid use and rheumatoid arthritis were predictors of an early fracture (< 2 years after inclusion). A shorter 'time to first fracture' was not an independent clinical risk factor for imminent fractures. PURPOSE: Risk factors for fragility fractures independent of BMD were assessed in several prediction models. However, predictors of a shorter 'time to first fracture' and its impact on imminent fractures are unknown. METHODS: We studied the concept of 'time to first fracture' in the FRISBEE ("Fracture RIsk Brussels Epidemiological Enquiry") cohort (3560 postmenopausal women). Validated fractures were divided into 3 groups: first fracture < 2 years, 2-5 years, and > 5 years after inclusion. Factors associated with first fracture risk were evaluated with uni- and multivariate analyses using Cox modeling. We examined 'time to first fracture' as a risk factor for imminent fractures in untreated subjects and in those receiving pharmacological treatment. RESULTS: Classical risk factors (age, prior fracture, fall history and low BMD) were associated with first fracture in all groups. Previous glucocorticoids and rheumatoid arthritis (RA) were predictors for fracture < 2 years. Imminent fractures were similar in subjects with or without osteoporosis treatment, despite a higher estimated 10-year risk of fragility fracture in those treated, suggesting that treatment is efficient. 'Time to first fracture' was not an independent risk factor for imminent fractures. CONCLUSION: Among the risk factors considered, previous glucocorticoid use and RA were predictors for early fracture, consistent with the concept of very high risk. The 'time to first validated fracture' was not an independent risk factor for imminent fractures. Patients with a first osteoporotic fracture should thus be considered at very high risk for re-fracture, independent of the 'time to first fracture'.

External validation of FRISBEE 5-year fracture prediction models: a registry-based cohort study.

Five-year fracture risk prediction from the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) models was externally tested in 9716 Canadian women and demonstrated good discrimination but consistently overestimated risk. INTRODUCTION: Five-year risk prediction models for all fractures, major osteoporotic fractures (MOFs) and central fractures (proximal to forearm and ankle) from the FRISBEE cohort demonstrated good performance in the original derivation cohort. Our aim was to externally validate the FRISBEE-based 5-year prediction models in routine practice. METHODS: Using the population-based Manitoba Bone Mineral Density (BMD) registry, we identified women aged 60-85 years undergoing baseline BMD assessment from September 1, 2012 to March 31, 2018. Five-year probabilities of all fractures, MOFs and central fractures were calculated using the FRISBEE prediction models. We identified incident non-traumatic fractures up to 5 years from population-based healthcare data sources. Performance characteristics included area under the receiver operating characteristic curve (AUROC), gradient of risk (hazard ratio [HR] per SD increase and across risk tertiles) from Cox regression analysis, and calibration (ratio 5-year observed cumulative incidence to predicted fracture probability). RESULTS: We included 9716 women (mean age 70.7 + / - SD 5.3 years). During a mean observation time of 2.5 years, all fractures, MOFs and central fractures were identified in 377 (3.9%), 264 (2.7%) and 259 (2.7%) of the women. AUROC showed significant fracture risk stratification with the FRISBEE models (all fractures 0.69 [95%CI 0.67-0.72], MOFs 0.71 [95%CI 0.68-0.74], central fractures 0.72 [95%CI 0.69-0.75]). There was a strong gradient of risk for predicting fracture outcomes per SD increase (HRs from 1.98 to 2.26) and across risk tertiles (HRs for middle vs lowest from 2.25 to 2.41, HRs for highest vs lowest from 4.70 to 6.50). However, risk was overestimated for all fractures (calibration-in-the-large 0.63, calibration slope 0.63), MOF (calibration-in-the-large 0.51, calibration slope 0.57) and central fractures (calibration-in-the-large 0.55, calibration slope 0.60). CONCLUSIONS: FRISBEE 5-year prediction models were externally validated to stratify fracture risk similar to the derivation cohort, but would need recalibration for Canada as risk was overestimated.

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club.

Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed.

Fragility Fractures in Postmenopausal Women: Development of 5-Year Prediction Models Using the FRISBEE Study.

CONTEXT: Individualized fracture risk may help to select patients requiring a pharmacological treatment for osteoporosis. FRAX and the Garvan fracture risk calculators are the most used tools, although their external validation has shown significant differences in their risk prediction ability. OBJECTIVE AND METHODS: Using data from the Fracture Risk Brussels Epidemiological Enquiry study, a cohort of 3560 postmenopausal women aged 60 to 85 years, we aimed to construct original 5-year fracture risk prediction models using validated clinical risk factors (CRFs). Three models of competing risk analysis were developed to predict major osteoporotic fractures (MOFs), all fractures, and central fractures (femoral neck, shoulder, clinical spine, pelvis, ribs, scapula, clavicle, sternum). RESULTS: Age, a history of fracture, and hip or spine BMD were predictors common to the 3 models. Excessive alcohol intake and the presence of comorbidities were specific additional CRFs for MOFs, a history of fall for all fractures, and rheumatoid arthritis for central fractures. Our models predicted the fracture probability at 5 years with an acceptable accuracy (Brier scores ≤ 0.1) and had a good discrimination power (area under the receiver operating curve of 0.73 for MOFs and 0.72 for central fractures) when internally validated by bootstrap. Three simple nomograms, integrating significant CRFs and the mortality risk, were constructed for different fracture sites. In conclusion, we derived 3 models predicting fractures with an acceptable accuracy, particularly for MOFs and central fractures. The models are based on a limited number of CRFs, and we constructed nomograms for use in clinical practice.

Prediction of an Imminent Fracture After an Index Fracture - Models Derived From the Frisbee Cohort.

Patients who sustain a fracture are at greatest risk of recurrent fracture during the next 2 years. We propose three models to identify subjects most at risk of an imminent fracture, according to fracture site (any fracture, major osteoporotic fracture [MOF] or central). They were constructed using data of the prospective Frisbee cohort, which includes 3560 postmenopausal women aged 60 to 85 years who were followed for at least 5 years. A total of 881 subjects had a first incident validated fragility fracture before December 2018. Among these, we validated 130 imminent fractures occurring within the next 2 years; 79 were MOFs, and 88 were central fractures. Clinical risk factors were re-evaluated at the time of the index fracture. Fine and Gray proportional hazard models were derived separately for each group of fractures. The following risk factors were significantly associated with the risk of any imminent fracture: total hip bone mineral density (BMD) (p < 0.001), a fall history (p < 0.001), and comorbidities (p = 0.03). Age (p = 0.05 and p = 0.03, respectively) and a central fracture as the index fracture (p = 0.04 and p = 0.005, respectively) were additional predictors of MOFs and central fractures. The three prediction models are presented as nomograms. The calibration curves and the Brier scores based on bootstrap resampling showed calibration scores of 0.089 for MOF, 0.094 for central fractures, and 0.132 for any fractures. The predictive accuracy of the models expressed as area under the receiver operating characteristic (AUROC) curve (AUC) were 0.74 for central fractures, 0.72 for MOFs, and 0.66 for all fractures, respectively. These AUCs compare well with those of FRAX and Garvan to predict the 5- or 10-year fracture probability. In summary, five predictors (BMD, age, comorbidities, falls, and central fracture as the incident fracture) allow the calculation with a reasonable accuracy of the imminent risk of fracture at different sites (MOF, central fracture, and any fracture) after a recent sentinel fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).

Independent External Validation of FRAX and Garvan Fracture Risk Calculators: A Sub-Study of the FRISBEE Cohort.

Probabilistic models including clinical risk factors with or without bone mineral density (BMD) have been developed to estimate the 5- or 10-year absolute fracture risk. We investigated the performance of the FRAX and Garvan tools in a well-characterized population-based cohort of 3560 postmenopausal, volunteer women, aged 60 to 85 years at baseline, included in the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) cohort, during 5 years of follow-up. Baseline data were used to calculate the estimated 10-year risk of hip and major osteoporotic fractures (MOFs) for each participant using FRAX (Belgium). We computed the 5-year risk according to the Garvan model with BMD. For calibration, the predicted risk of fracture was compared with fracture incidence across a large range of estimated fracture risks. The accuracy of the calculators to predict fractures was assessed using the area under the receiver operating characteristic curves (AUC). The FRAX tool was well calibrated for hip fractures (slope 1.09, p < 0.001; intercept -0.001, p = 0.46), but it consistently underestimated the incidence of major osteoporotic fractures (MOFs) (slope 2.12, p < 0.001; intercept -0.02, p = 0.06). The Garvan tool was well calibrated for "any Garvan" fractures (slope 1.05, p < 0.001; intercept 0.01, p = 0.37) but largely overestimated the observed hip fracture rate (slope 0.32, p < 0.001; intercept 0.006, p = 0.05). The predictive value for hip fractures was better for FRAX (AUC: 0.841, 95% confidence interval [CI] 0.795-0.887) than for Garvan (AUC: 0.769, 95% CI 0.702-0.836, p = 0.01). The Garvan AUC for "any Garvan" fractures was 0.721 (95% CI 0.693-0.749) and FRAX AUC for MOFs was 0.708 (95% CI 0.675-0.741). In conclusion, in our Belgian cohort, FRAX estimated quite well hip fractures but underestimated MOFs, while Garvan overestimated hip fracture risk but showed a good estimation of "any Garvan" fractures. Both models had a good discriminatory value for hip fractures but only a moderate discriminatory ability for MOFs or "any Garvan" fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A rare cause of persistent hyperparathyroidism.

In a case of patient with persistent hypercalcemia after parathyroidectomy, different imaging techniques and particularly 18F-fluorocholine PET/CT are important to localize the adenoma even in a very unusual location.

Can we safely reduce the administration of 131-iodine in patients with differentiated thyroid cancer? - experience of the Brugmann hospital in Brussels.

BACKGROUND: 131-iodine (131I) administration after surgery remains a standard practice in differentiated thyroid cancer (DTC). In 2014, the American Thyroid Association presented new guidelines for the staging and management of DTC, including no systematic 131I in patients at low-risk of recurrence and a reduced 131I activity in intermediate risk.The present study aims at evaluating the rate of response to treatment following this new therapeutic management compared to our previous treatment strategy in patients with DTC of different risks of recurrence. METHODS: Patients treated and followed up for DTC according to the 2014-ATA guidelines (Group 2) were compared to those treated between 2007 and 2014 (Group 1) in terms of general characteristics, risk of recurrence (based on the 2015-ATA recommendations), preparation to 131I administration, cumulative administered 131I activity and response to treatment. RESULTS: In total, 136 patients were included: 78 in Group 1 and 58 in Group 2. The two groups were not statistically different in terms of clinical characteristics nor risk stratification: 42.3% in Group 1 and 31% in Group 2 were classified as low risk, 38.5 and 48.3% as intermediate risk and 19.2 and 20.7% as high risk (P = 0.38). Two patients (one in each group) with distant metastases were excluded from the analysis.Preparation to 131I administration consisted in rhTSH stimulation in 23.4% of the patients in Group 1 and 100% in Group 2 (p < 0.001).131I was administered to 46/77 patients (59.7%) in Group 1 (5 at low risk of recurrence) and 38/57 patients (66.7%) in Group 2 (0 with a low risk). Among the patients treated by 131I, median cumulative activity was significantly higher in Group 1 (3.70GBq [100 mCi] range 1.11-11.1 GBq [30-300 mCi]) than in Group 2 (1.11 GBq [30 mCi], range 1.11-7.4 GBq [30-200 mCi], P < 0.001). Complete response was found in 90.9% in Group 1 vs. 96.5% in Group 2 (P = 0.20). CONCLUSIONS: Using the 2015-ATA evidence-based guidelines for the management of DTC, meaning no 131I administration in low-risk patients, a low activity in intermediate and even high risk patients, and a systematic use of rhTSH stimulation before 131I therapy allowed us to reduce significantly the median administered 131I activity, with a similar rate of complete therapeutic response.

Underevaluation of fractures by self-report: an analysis from the FRISBEE cohort.

We assessed the rate of non-reported fractures in the FRISBEE cohort. Over a median follow-up period of 9.2 years, we registered 992 fractures. The global percentage of non-reported fractures was 21.3%. Underreporting of fracture event might influence any model of fracture risk prediction. INTRODUCTION: Most fracture cohort studies rely on participant self-report of fracture event. This approach may lead to fracture underreporting. The purpose of the study was to assess the rate of non-reported fractures in a well-characterized population-based cohort of 3560 postmenopausal women, aged 60-85 years, included in the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) study. METHODS: Incident low-traumatic or non-traumatic fractures were registered annually during phone calls. In 2018, we reviewed the medical files of 67.9% of our study participants and identified non-reported fractures ("false negatives fractures (FN)"). We also evaluated whether the rate of FN was influenced by baseline patients' characteristics and fracture risk factors. Generalized estimating equation (GEE) was used to calculate odds ratio (OR) and 95% CI. RESULTS: Over a median follow-up period of 9.2 years, we registered 992 fractures (781 by self-report, confirmed by a radiological report and 211 unreported). The global false negative rate for all fractures was 21.3%, including 22% for MOFs (major osteoporotic fractures), 13.1% for other major fractures, and 25.8% for minor fractures. The rate of non-reported fractures varied by fracture site: for MOFs, it was 2.7% (n = 2/73) at the hip, 5.3% at the proximal humerus (n = 5/94), 7.1% at the wrist (n = 11/154), and 46.5% at the spine (n = 100/215). For "other major" fractures, the highest rate of false negatives fractures was found at the pelvic bone (21%, n = 13/62), followed by the elbow (17.9%, n = 5/28), long bones (10.5%, n = 2/19), ankle (6.2%, n = 4/65), and knee (5.9%, n = 1/17). Older subjects (OR 1.7; 95% CI, 1.2-2.4; P = 0.003), subjects with early non-substituted menopause (OR 1.8; 95% CI, 1.0-3.3; P = 0.04), with a lower education level (OR 1.5; 95%CI, 1.1-2.2; P = 0.01), and those under drug therapy for osteoporosis (OR 1.5; 95% CI, 1.0-2.2; P = 0.05) were associated with a higher rate of FN. CONCLUSIONS: In conclusion, underreporting of a substantial proportion of fracture events will influence any model of fracture risk prediction and induce bias when estimating the associations between candidate risk factors and incident fractures.

Assessment of bone quality with trabecular bone score in type 2 diabetes mellitus: A study from the FRISBEE cohort.

OBJECTIVE: The purpose of our study was to compare bone mineral density (BMD) and trabecular bone score (TBS) values between patients with type 2 diabetes (T2D) and control subjects with similar FRAX scores in order to evaluate TBS as an additional tool for assessing fracture risk in diabetic subjects. METHODS: A cross-sectional analysis was performed using BMD results from 260 subjects participating in the FRISBEE study (Fracture RISk Brussels Epidemiological Enquiry), an ongoing prospective epidemiological study in a population-based cohort (Brussels, Belgium) of 3560 postmenopausal women aged 60-85 years. TBS measurement was possible in 1108 subjects from the FRISBEE cohort. Among these 1108 subjects, 65 had known T2D at inclusion. For each diabetic case we selected 3 controls from our database. (n = 195). Diabetic subjects and controls were matched for age and baseline FRAX score for major osteoporotic fractures. RESULTS: BMD (g/cm2 ) tended to be higher in T2D than in control subjects, significantly so at the total hip 0.90 ± 0.13 versus 0.87 ± 0.12 (P = 0.015). On the contrary, TBS was significantly lower in the T2D group (mean = 1.19 ± 0.17) compared with the control group (mean = 1.27 ± 0.13) (P = 0.005). Mean TBS remained significantly lower in T2D (1.22 ± 0.17) compared with the control group (1.27 ± 0.13) (P = 0.02) after adjustment for body mass index. CONCLUSION: Our data suggest that TBS complements BMD at the total hip, in demonstrating the "diabetes-associated bone disease".

Skeletal health in breast cancer survivors.

Although some risk factors for breast cancer might be protective for osteoporosis, several cross-sectional studies have reported, nevertheless, that patients with breast cancer have a lower bone mass and potentially a higher incidence of fractures than expected. In any case, it appears that patients with breast cancer are not protected from osteoporosis, which provides further support for the recommendation that bone health is assessed after a diagnosis of breast cancer. Most adjuvant therapies will lead to increased bone loss and a higher fracture rate. Among the adjuvant therapy options for premenopausal patients with breast cancer, endocrine therapy (ovarian suppression) and chemotherapy can result in cancer treatment-induced bone loss (CTIBL) of up to 10% at the lumbar spine after one year. Antiresorptive therapies prevent CTIBL in premenopausal women with breast cancer. Most of the evidence demonstrating the efficacy of bisphosphonates in the prevention of CTIBL is derived from clinical trials with zoledronic acid. The addition of zoledronic acid 4mg per six months to adjuvant endocrine therapy maintained and even increased bone mass during a 3-year treatment period and significantly improved disease-free survival in a population of young women who underwent menopause due to the adjuvant treatment. The major contributor to bone loss in the adjuvant treatment of breast cancer in postmenopausal women is the use of aromatase inhibitors (AIs). Oncology trials have underestimated the fracture risk in the setting of AI-induced bone loss. In the ABCSG-18 study, the only trial in which fracture incidence was the primary endpoint, the rate of clinical fractures was close to 10% after 3 years in the placebo group on AIs only. Bisphosphonates and denosumab at osteoporosis treatment doses can counteract AI-induced bone loss. In the ABCSG-18 trial, treatment with denosumab 60mg injection every 6 months reduced the risk of first clinical fracture relative to placebo by 50%. Current guidelines recommend antiresorptive therapy in patients with a baseline T score of <-2.0 or with two or more clinical risk factors for fracture. These recent guidelines will need to be updated, as similar significant protective effects were seen in women with either normal or low bone mass. Moreover, a formal meta-analysis of individual patient data from more than 18,000 women in 26 randomized trials of adjuvant zoledronic acid or clodronate treatment for early breast cancer revealed that bisphosphonates significantly reduced the risk of first distant recurrence in bone and the risk of breast cancer mortality, at least in postmenopausal women. Even though the increased risk of fracture during adjuvant treatment for breast cancer in postmenopausal women is notable, an enhanced risk of fracture in long-term survivors of breast cancer remains under debate. The most recent studies suggest that Caucasian breast cancer survivors do not have a significantly increased risk of osteoporotic fracture over the long term.

Inflammation induced by inhaled lipopolysaccharide depends on particle size in healthy volunteers.

AIMS: In drug development, the anti-inflammatory properties of new molecules in the lung are currently tested using the inhaled lipopolysaccharide (LPS) model. The total and regional lung bioavailability of inhaled particles depends significantly on their size. The objective of the present study was to compare inflammatory responses in healthy volunteers after the inhalation of LPS of varying droplet size. METHODS: Three nebulizers were characterized by different droplet size distributions [mean mass median aerodynamic diameters: Microcirrus (2.0 µm), MB2 (3.2 µm) and Pari (7.9 µm)]. Participants inhaled three boluses of a 20 µg (technetium 99 m-labelled) solution of LPS, randomly delivered by each nebulizer. We measured the lung deposition of the nebulized LPS by gamma-scintigraphy, while blood and sputum biomarkers were evaluated before and after challenges. RESULTS: MB2 and Pari achieved greater lung deposition than Microcirrus [171.5 (±72.9) and 217.6 (±97.8) counts pixel-1 , respectively, vs. 67.9 (±20.6) counts pixel-1 ; P < 0.01]. MB2 and Pari caused higher levels of blood C-reactive protein and more total cells and neutrophils in sputum compared with Microcirrus (P < 0.05). C-reactive protein levels correlated positively with lung deposition (P < 0.01). CONCLUSIONS: Inhalation of large droplets of LPS gave rise to greater lung deposition and induced a more pronounced systemic and bronchial inflammatory response than small droplets. The systemic inflammatory response correlated with lung deposition. NCT01081392.

Effects of Dairy Products Consumption on Health: Benefits and Beliefs--A Commentary from the Belgian Bone Club and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases.

Dairy products provide a package of essential nutrients that is difficult to obtain in low-dairy or dairy-free diets, and for many people it is not possible to achieve recommended daily calcium intakes with a dairy-free diet. Despite the established benefits for bone health, some people avoid dairy in their diet due to beliefs that dairy may be detrimental to health, especially in those with weight management issues, lactose intolerance, osteoarthritis, rheumatoid arthritis, or trying to avoid cardiovascular disease. This review provides information for health professionals to enable them to help their patients make informed decisions about consuming dairy products as part of a balanced diet. There may be a weak association between dairy consumption and a possible small weight reduction, with decreases in fat mass and waist circumference and increases in lean body mass. Lactose intolerant individuals may not need to completely eliminate dairy products from their diet, as both yogurt and hard cheese are well tolerated. Among people with arthritis, there is no evidence for a benefit to avoid dairy consumption. Dairy products do not increase the risk of cardiovascular disease, particularly if low fat. Intake of up to three servings of dairy products per day appears to be safe and may confer a favourable benefit with regard to bone health.

Health technology assessment in osteoporosis.

We review the various aspects of health technology assessment in osteoporosis, including epidemiology and burden of disease, and assessment of the cost-effectiveness of recent advances in the treatment of osteoporosis and the prevention of fracture, in the context of the allocation of health-care resources by decision makers in osteoporosis. This article was prepared on the basis of a symposium held by the Belgian Bone Club and the discussions surrounding that meeting and is based on a review and critical appraisal of the literature. Epidemiological studies confirm the immense burden of osteoporotic fractures for patients and society, with lifetime risks of any fracture of the hip, spine, and forearm of around 40 % for women and 13 % for men. The economic impact is also large; for example, Europe's six largest countries spent €31 billion on osteoporotic fractures in 2010. Moreover, the burden is expected to increase in the future with demographic changes and increasing life expectancy. Recent advances in the management of osteoporosis include novel treatments, better fracture-risk assessment notably via fracture risk algorithms, and improved adherence to medication. Economic evaluation can inform decision makers in health care on the cost-effectiveness of the various interventions. Cost-effectiveness analyses suggest that the recent advances in the prevention and treatment of osteoporosis may constitute an efficient basis for the allocation of scarce health-care resources. In summary, health technology assessment is increasingly used in the field of osteoporosis and could be very useful to help decision makers efficiently allocate health-care resources.

Extensive peritoneal uptake of technetium-99m-labelled hydroxy diphosphonate in a patient undergoing hemodialysis.

A 48-year-old African lady started peritoneal dialysis in 1994 after transplant failure. After several episodes of peritonitis and hemorrhagic ascites, hemodialysis was resumed in 2003 because of small bowel subocclusion. In 2006, an abdominal CT showed calcifications and dilatation of intestinal loops. Sclerosing peritonitis was diagnosed and she underwent enterolysis and resection of the peritoneal capsule. She remained asymptomatic until 2009 when she presented again with subocclusion. Because of generalized skeletal pain, a bone scan was performed, which showed Tc-99m hydroxy diphosphonate uptake on the peritoneum. The patient is currently on hemodialysis with parenteral nutrition.

Effects on muscle performance of NSAID treatment with piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. A double blind randomized controlled trial.

BACKGROUND: Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp. METHODS: Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation. RESULTS: EMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group. CONCLUSIONS: Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may include modifications in the cytokine network and increases in monocytic expression of cytoprotective Hsp27. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN96340690.

Plasma osteoprotegerin is an independent risk factor for mortality and an early biomarker of coronary vascular calcification in chronic kidney disease.

BACKGROUND: Cardiovascular disease is the major cause of morbidity and mortality in chronic kidney disease (CKD) and early biomarkers are required which can predict disease and death in such patients. The aim of our study was to investigate if osteoprotegerin (OPG) could be a predictor of coronary artery calcification (CAC) and mortality in CKD. METHODS: A total of 77 outpatients (32 with pre-dialysis CKD and 45 undergoing hemodialysis) were followed-up during 2 years. Measurements of CAC were performed using Siemens Multidetector CT software and calcium scores were measured according to the Agatston method. RESULTS: OPG was an independent predictor of the Agatston score for CAC and correlated with the degree of CAC in pre-dialysis patients. A two-sample t-test characterized survivors as having a better glomerular filtration rate, lower Agatston scores, and lower serum levels of OPG. Kaplan-Meier survival curves separated survivors from non-survivors at plasma OPG cut-off levels of <3.1 ng/mL. A multivariable logistic regression analysis showed that OPG was an independent predictor of mortality from all causes in CKD patients. CONCLUSIONS: OPG predicted mortality in CKD patients and could be a valuable biomarker in early detection of CAC in these patients.