Thierry Thomas

The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS)--quality of life during the first 4 months after fracture.

SummaryThe quality of life during the first 4 months after fracture was estimated in 2,808 fractured patients from 11 countries. Analysis showed that there were significant differences in the quality of life (QoL) loss between countries. Other factors such as QoL prior fracture and hospitalisation also had a significant impact on the QoL loss.IntroductionThe International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) was initiated in 2007 with the objective of estimating costs and quality of life related to fractures in several countries worldwide. The ICUROS is ongoing and enrols patients in 11 countries (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, UK and the USA). The objective of this paper is to outline the study design of ICUROS and present results regarding the QoL (measured using the EQ-5D) during the first 4xa0months after fracture based on the patients that have been thus far enrolled ICUROS.MethodsICUROS uses a prospective study design where data (costs and quality of life) are collected in four phases over 18xa0months after fracture. All countries use the same core case report forms. Quality of life was collected using the EQ-5D instrument and a time trade-off questionnaire.ResultsThe total sample for the analysis was 2,808 patients (1,273 hip, 987 distal forearm and 548 vertebral fracture). For all fracture types and countries, the QoL was reduced significantly after fracture compared to pre-fracture QoL. A regression analysis showed that there were significant differences in the QoL loss between countries. Also, a higher level of QoL prior to the fracture significantly increased the QoL loss and patients who were hospitalised for their fracture also had a significantly higher loss compared to those who were not.ConclusionsThe findings in this study indicate that there appear to be important variations in the QoL decrements related to fracture between countries.

Identification and management of patients at increased risk of osteoporotic fracture: Outcomes of an ESCEO expert consensus meeting

SummaryOsteoporosis represents a significant and increasing healthcare burden in Europe, but most patients at increased risk of fracture do not receive medication, resulting in a large treatment gap. Identification of patients who are at particularly high risk will help clinicians target appropriate treatment more precisely and cost-effectively, and should be the focus of future research.IntroductionThe purpose of the study was to review data on the identification and treatment of patients with osteoporosis at increased risk of fracture.MethodsA working group convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review current data on the epidemiology and burden of osteoporosis and the patterns of medical management throughout Europe.ResultsIn Europe in 2010, the cost of managing osteoporosis was estimated at €37 billion and notably the costs of treatment and long-term care of patients with fractures were considerably higher than the costs for pharmacological prevention. Despite the availability of effective treatments, the uptake of osteoporosis therapy is low and declining, in particular for secondary fracture prevention where the risk of a subsequent fracture following a first fracture is high. Consequently, there is a significant treatment gap between those who would benefit from treatment and those who receive it, which urgently needs to be addressed so that the burden of disease can be reduced.ConclusionsImplementation of global fracture prevention strategies is a critical need. Future research should focus on identifying specific risk factors for imminent fractures, periods of high fracture risk, patients who are at increased risk of fracture and therapies that are most suited to such high-risk patients and optimal implementation strategies in primary, secondary and tertiary care.

High prevalence of dementia in women with osteoporosis

INTRODUCTIONnAlzheimers disease or other Dementias (ADD) and postmenopausal osteoporosis are two major public health problems with a huge impact on mortality. Here, we examined the prevalence of ADD in postmenopausal women with osteoporosis, monitored within a dedicated fracture liaison service.nnnMETHODSnWe conducted a cross-sectional observational study in a population of 2041 women, visiting the university hospital of Saint-Etienne for a peripheral fragility fracture. We assessed the prevalence of ADD among these patients and compared to French population. We also compared the characteristics of women with ADD and without ADD.nnnRESULTSnADD prevalence was on average 13.5% in the population of interest with a mean age of 85years. As women with ADD were older than women without ADD, the prevalence of the disease significantly increased with age as 0%, 1.8%, 13% and 29.7% in<55, 55-74, 75-79 and 85-89years old groups, respectively. Proximal femoral fracture was the most frequent fracture (77%) followed by wrist fracture (13%), and then proximal humerus fracture (10%). ADD prevalence observed in our study was 3 to 4 times the ADD prevalence in France. Despite the overall increase of the ADD prevalence with age, it was still 2.2 and 1.9 times that of the French female population in the 80-84 and 85-89 age groups respectively.nnnCONCLUSIONnADD prevalence was higher in postmenopausal women with severe osteoporosis, especially those with femoral fractures. Thus, our results incite to a more efficient care of this population with a high risk of fracture and mortality.

Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease

The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft ‘Guideline on clinical investigation of medicinal products for the treatment of RA’ released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1u2005year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria.

Cortical and trabecular bone microstructure did not recover at weight-bearing skeletal sites and progressively deteriorated at non-weight-bearing sites during the year following International Space Station missions†

Risk for premature osteoporosis is a major health concern in astronauts and cosmonauts; the reversibility of the bone lost at the weight‐bearing bone sites is not established, although it is suspected to take longer than the mission length. The bone three‐dimensional structure and strength that could be uniquely affected by weightlessness is currently unknown. Our objective is to evaluate bone mass, microarchitecture, and strength of weight‐bearing and non‐weight‐bearing bone in 13 cosmonauts before and for 12 months after a 4‐month to 6‐month sojourn in the International Space Station (ISS). Standard and advanced evaluations of trabecular and cortical parameters were performed using high‐resolution peripheral quantitative computed tomography. In particular, cortical analyses involved determination of the largest common volume of each successive individual scan to improve the precision of cortical porosity and density measurements. Bone resorption and formation serum markers, and markers reflecting osteocyte activity or periosteal metabolism (sclerostin, periostin) were evaluated. At the tibia, in addition to decreased bone mineral densities at cortical and trabecular compartments, a 4% decrease in cortical thickness and a 15% increase in cortical porosity were observed at landing. Cortical size and density subsequently recovered and serum periostin changes were associated with cortical recovery during the year after landing. However, tibial cortical porosity or trabecular bone failed to recover, resulting in compromised strength. The radius, preserved at landing, unexpectedly developed postflight fragility, from 3 months post‐landing onward, particularly in its cortical structure. Remodeling markers, uncoupled in favor of bone resorption at landing, returned to preflight values within 6 months, then declined farther to lower than preflight values. Our findings highlight the need for specific protective measures not only during, but also after spaceflight, because of continuing uncertainties regarding skeletal recovery long after landing.

High bone turnover persisting after vitamin D repletion: beware of calcium deficiency

Treatment of vitamin D deficiency with vitamin D is a common procedure when taking care of elderly patients, calcium supplementation being added only when calcium dietary intake is insufficient. Here, we report the case of a 58-year-old female who was referred to our unit because of suspicion of Paget’s disease of the skull, based on elevated serum alkaline phosphatase and high skull methylene diphosphonate-technetium uptake. She had been prescribed cholecalciferol (100,000xa0IU/month) and calcium salts for the past 7xa0months after discovery of severe vitamin D deficiency by her primary care physician. No specific skull bone lesions were observed on both X-ray and computerized tomography. Serum calcium, phosphate and 25(OH) vitamin D levels were normal, while serum C-terminal cross-linked telopeptide, bone alkaline phosphatase and calcitriol were high and daily urinary calcium excretion was low. We found that she had not been compliant with the calcium prescription while vitamin D had been thoroughly taken. We suspected osteomalacia due to calcium deficiency. Both skull uptake and biological abnormalities normalised in few months after adding calcium supplementation to the vitamin D treatment, and spine bone mineral density increased by 9.5xa0% after 14xa0months of full treatment. The present case illustrates the necessity for adequate calcium intake during vitamin D repletion to normalise bone mineralisation and turnover and maintain the skeletal integrity.

Spectacular improvement in vitamin D status in elderly osteoporotic women: 8-year analysis of an osteoporotic population treated in a dedicated fracture liaison service

SummaryIn a population of postmenopausal women with a fragility fracture, we found a drastic reduction in the proportion of women with severe (<25xa0nmol/L) and moderate (25 to 75xa0nmol/L) hypovitaminosis D, especially from 2009 onwards. These results show that supplementation has been very widely integrated into current practice.IntroductionVitamin D (25(OH)D) is essential for bone health. In institutionalised osteoporotic women, it reduces the risk of fragility fractures. Numerous articles suggesting the possibility of extraosseous effects have generated a growing number of publications and recommendations on more widespread administration, to limit the risks of moderate or severe hypovitaminosis D. We assessed the impact on clinical practice of these recommendations concerning 25(OH)D supplementation in elderly at-risk populations.MethodsA total of 1486 postmenopausal osteoporotic women were seen in the context of a fracture liaison service (i.e. a rheumatology consultation following a peripheral fragility fracture), between May 2005 and December 2012. Of these, 1107 had a 25(OH)D assay (femur, nu2009=u2009520; humerus, nu2009=u2009207; wrist, nu2009=u2009380).ResultsThe average age of the total population was 76.7u2009±u20099.9xa0years, while for women with an available 25(OH)D assay, the average age was 75.1u2009±u200911.8xa0years. The average 25(OH)D (nmol/L) level was similar for the three fracture sites: femur, 30u2009±u200936.2; humerus, 27.5u2009±u200924; and wrist, 31u2009±u200926. A drastic reduction in the proportion of women with severe (<25xa0nmol/L) and moderate (25 to 75xa0nmol/L) hypovitaminosis D was observed, especially from 2009 onwards, with a mean prevalence of 69 and 30xa0% respectively before that year and 35 and 52xa0% thereafter. Conversely, the proportion of women with 25(OH)D at the threshold value of 75xa0nmol/L increased from 1.2 to 24xa0%. Overall, mean serum 25(OH)D levels were significantly higher when comparing the two periods 2005–2008 and 2009–1012 (17.6u2009±u200914.6 and 48.4u2009±u200939.2xa0nmol/L, respectively; pu2009<u20090.0001).ConclusionThese results show that supplementation has been very widely integrated into current practice. We can expect it to yield beneficial effects in osseous and extraosseous terms in osteoporotic women, particularly the very elderly.

A6.7 Evaluation of porphyromonas gingivalis serology in rheumatic and non-rheumatic inflammatory disease

Objectives Porphyromonas gingivalis (P. gingivalis) interest for RA development disease is growing fast since it is the only bacteria able to citrullinate peptides and may induce autoimmune response through development of ACPA. However, few studies have reported its presence in others inflammatory diseases. The aim of this study is to evaluate the specificity of P. gingivalis and Prevotella intermedia (P. intermedia) serology in patients with rheumatic diseases including rheumatoid arthritis (RA) and spondylarthritis (SA) compared to controls (healthy subjects or patients with inflammatory bowel disease (IBD)). Methods We enrolled in this study 79 RA patients, 56 SA patients and 39 IBD patients requiring infliximab therapy, as well as 30 healthy controls. Anti-P. intermedia antibodies and anti-P. gingivalis LPS specific and whole extract antibodies were determined by ELISA. Specificity of these antibodies was evaluated by the search for antibodies against a commensal bacterium of the intestinal tract: Escherichia Coli (E. coli). Results Anti-P. gingivalis antibody titers determined by LPS and whole extract were well correlated together (P < 0.0001) as well as antibody titers against the two oral bacteria (P. gingivalis and P. intermedia) (P < 0.0001). By using LPS from E. coli, no cross reaction was observed as high anti-P. gingivalis antibody titers were negative for anti-E. coli antibody and vice versa. Anti-P. gingivalis antibodies titers were higher in RA and SA patients than in healthy subjects (P < 0.0001) or in IBD patients (P< 0.0001). Moreover, there was a trend for higher titers in RA patients than in SA patients (Fig 1A). Same results were found with anti-P. intermedia antibody titers which were higher in RA and SA patients than in healthy controls (P < 0.0001) or IBD patients (P < 0.0001) (Fig 1B). Conclusions P. gingivalis and P. intermedia are oral bacteria having an important role in rheumatic diseases, especially in RA, compared to another inflammatory disease as shown by higher titers of antibodies found in both RA and SA.

Quality of life after hip, vertebral, and distal forearm fragility fractures measured using the EQ-5D-3L, EQ-VAS, and time-trade-off: results from the ICUROS

IntroductionThe International Costs and Utilities Related to Osteoporotic fractures Study is a multinational observational study set up to describe the costs and quality of life (QoL) consequences of fragility fracture. This paper aims to estimate and compare QoL after hip, vertebral, and distal forearm fracture using time-trade-off (TTO), the EuroQol (EQ) Visual Analogue Scale (EQ-VAS), and the EQ-5D-3L valued using the hypothetical UK value set.MethodsData were collected at four time-points for five QoL point estimates: within 2xa0weeks after fracture (including pre-fracture recall), and at 4, 12, and 18xa0months after fracture. Health state utility values (HSUVs) were derived for each fracture type and time-point using the three approaches (TTO, EQ-VAS, EQ-5D-3L). HSUV were used to estimate accumulated QoL loss and QoL multipliers.ResultsIn total, 1410 patients (505 with hip, 316 with vertebral, and 589 with distal forearm fracture) were eligible for analysis. Across all time-points for the three fracture types, TTO provided the highest HSUVs, whereas EQ-5D-3L consistently provided the lowest HSUVs directly after fracture. Except for 13–18xa0months after distal forearm fracture, EQ-5D-3L generated lower QoL multipliers than the other two methods, whereas no equally clear pattern was observed between EQ-VAS and TTO. On average, the most marked differences between the three approaches were observed immediately after the fracture.ConclusionsThe approach to derive QoL markedly influences the estimated QoL impact of fracture. Therefore the choice of approach may be important for the outcome and interpretation of cost-effectiveness analysis of fracture prevention.

Quality of life for up to 18 months after low-energy hip, vertebral, and distal forearm fractures—results from the ICUROS

SummaryThis study used data from the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) to estimate the quality of life (QoL) impact of fracture. Hip, vertebral, and distal forearm fractures incur substantial QoL losses. Hip and vertebral fracture results in markedly impaired QoL for at least 18xa0months.IntroductionThe International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) is a multinational observational study that aims to describe costs and quality of life (QoL) consequences of osteoporotic fractures. To date, 11 countries have participated in the study: Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, the UK, and the USA. The objective of this paper is to describe the QoL impact of hip, vertebral, and distal forearm fracture.MethodsData were collected at four time-points for five QoL point estimates: within 2xa0weeks after fracture (including pre-fracture recall) and at 4, 12, and 18xa0months after fracture. Quality of life was measured as health state utility values (HSUVs) derived from the EQ-5D-3L. Complete case analysis was conducted as the base case with available case and multiple imputation performed as sensitivity analyses. Multivariate analysis was performed to explore predictors of QoL impact of fracture.ResultsAmong 5456 patients enrolled using convenience sampling, 3021 patients were eligible for the base case analysis (1415 hip, 1047 distal forearm, and 559 vertebral fractures). The mean (SD) difference between HSUV before and after fracture for hip, vertebral, and distal forearm fracture was estimated at 0.89 (0.40), 0.67 (0.45), and 0.48 (0.34), respectively (pu2009<u20090.001 for all fracture types). Eighteen months after fracture, mean HSUVs were lower than before the fracture in patients with hip fracture (0.66 vs. 0.77 pu2009<u20090.001) and vertebral fracture (0.70 vs. 0.83 pu2009<u20090.001). Hospitalization and higher recalled pre-fracture QoL were associated with increased QoL impact for all fracture types.ConclusionsHip, vertebral, and distal forearm fractures incur substantial loss in QoL and for patients with hip or vertebral fracture, QoL is markedly impaired for at least 18xa0months.