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Summary Thalassemia-associated osteoporosis constitutes a major complication in patients with thalassemia. This review presents the existing studies on the treatment of thalassemia-associated osteoporosis and discusses the management of this debilitating complication. A brief presentation of the disease characteristics and pathogenetic mechanisms is also provided. The life expectancy of patients with thalassemia has increased markedly in recent years resulting in the aging of the population and the emergence of new comorbidities. The majority of patients with thalassemia have low bone mineral density and experience lifelong fracture rates as high as 71 %. The pathogenesis of thalassemia-associated osteoporosis (TAO) is multifactorial with anemia and iron overload playing crucial role in its development. Data concerning the prevention and treatment of TAO are extremely limited. We performed a literature research in Pubmed and Scopus to identify interventional studies evaluating the effects of various agents on TAO. Seventeen studies were retrieved. We present the results of these studies as well as a brief overview of TAO including presentation, pathogenesis, and management. Most of the studies identified are of poor quality, are not randomized controlled, and include small number of participants. There are no data concerning effects on fracture rates. Bisphosphonates are the most widely studied agents and among them zoledronic acid is the most well studied. Hormone replacement treatment (HRT) shows beneficial but small effects. Denosumab and strontium ranelate have each been evaluated in only a single study, while there are no data about the effects of anabolic agents. Given the increased life expectancy and the increase in fracture rates with age, more data about the management of TAO are warranted. Moreover, due to the need for lifelong management starting at young age, careful treatment plans which may include sequential treatment may often be required. However, currently, there are no relevant data available.

Summary Persistence with and adherence to osteoporosis therapy are critical for fracture reduction. This non-interventional study is evaluating medication-taking behavior of women with postmenopausal osteoporosis (PMO) receiving denosumab in Germany, Austria, Greece, and Belgium. Patients were representative of the PMO population and highly persistent with and adherent to denosumab at 12 months. Introduction Persistence with and adherence to osteoporosis therapy are important for optimal treatment efficacy, namely fracture reduction. This ongoing, non-interventional study will evaluate medication-taking behavior of women with postmenopausal osteoporosis (PMO) receiving denosumab in routine practice in four European countries. Methods The study enrolled women who had been prescribed subcutaneous denosumab (60 mg every 6 months) in accordance with prescribing information and local guidelines. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection. Adherence was defined as receiving two consecutive injections within 6 months ± 4 weeks of each other. Medication coverage ratio (MCR) was calculated using the time a patient was covered with denosumab, as assessed from prescription records. Treatment was assigned prior to and independently of enrollment; outcomes are recorded during routine practice. Results These planned 12-month interim analyses included data from 1500 patients from 141 sites. Mean age was 66.4–72.4 years, mean baseline total hip T-scores ranged from −2.0 to −2.1 and femoral neck T-scores from −2.2 to −2.6, and 30.7–62.1 % of patients had prior osteoporotic fracture. Persistence was 87.0–95.3 %, adherence 82.7–89.3 %, and MCR 91.3–95.4 %. In a univariate analysis, increased age, decreased mobility, and increased distance to the clinic were associated with significantly decreased persistence; parental history of hip fracture was associated with significantly increased persistence. Conclusions These data extend the real-world evidence regarding persistence with and adherence to denosumab, both of which are critical for favorable clinical outcomes, including fracture risk reduction.

SummaryPersistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium found that persistence with denosumab remains consistently high after 24 months in patients at high risk of fracture.PurposeContinued persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of clinical practice evaluated medication-taking behavior of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium and factors influencing persistence.MethodsSubcutaneous denosumab (60 mg every 6 months) was assigned according to prescribing information and local guidelines before and independently of enrollment; outcomes were recorded during routine practice for up to 24 months. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection and adherence as administration of subsequent injections within 6 months ± 4 weeks of the previous injection. Medication coverage ratio (MCR) was calculated as the proportion of time a patient was covered by denosumab. Associations between pre-specified baseline covariates and 24-month persistence were assessed using multivariable logistic regression.ResultsThe 24-month analyses included 1479 women (mean age 66.3–72.5 years) from 140 sites; persistence with denosumab was 75.1–86.0%, adherence 62.9–70.1%, and mean MCR 87.4–92.4%. No covariate had a significant effect on persistence across all four countries. For three countries, a recent fall decreased persistence; patients were generally older with chronic medical conditions. In some countries, other covariates (e.g., older age, comorbidity, immobility, and prescribing reasons) decreased persistence. Adverse drug reactions were reported in 2.3–6.9% patients.ConclusionsTwenty-four-month persistence with denosumab is consistently high among postmenopausal women in Europe and may be influenced by patient characteristics. Further studies are needed to identify determinants of low persistence.

Summary Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n  = 45) and risedronate (35 mg/week, n  = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

ObjectiveWe present the subanalysis of the Greek cohort of the Extended Forsteo Observational Study (ExFOS), a multicenter, non-interventional, prospective, observational study evaluating the effect of teriparatide on fractures, back pain (BP), health-related quality of life (HR-QoL), and safety and compliance, in patients with osteoporosis treated for up to 24 months, with a post-treatment follow-up of at least 18 months.DesignA total of 439 osteoporotic patients (92.2% female) were enrolled in Greece. New or worsened fractures, based on their physicians’ assessment, as well as patients’ self-assessment of HR-QoL and BP, compliance, and safety profile, were captured by validated questionnaires.ResultsIn the ExFOS Greek cohort, fracture rates were low and mean bone mineral density (BMD) was numerically improved. Compliance with teriparatide remained high throughout the study, with 81.5% of subjects completing treatment. Only 0.7% of patients reported discontinuation due to adverse effects. A sustainable improvement in patient-perceived BP and HRQoL throughout treatment and follow-up was similar to that achieved by the European Forsteo Observational Study (EFOS). A lower than expected percentage of patients using antiresorptives following teriparatide was recorded.ConclusionsExFOS reproduces the outcomes of EFOS, with a 6.5-year time interval between studies, in comparable cohorts of osteoporotic patients. Data should be interpreted in the context of observational study data collection, although summary statistics computed at each time point may overstate drug effect.

Background Denosumab (DMAb) reduces the risk of new vertebral, nonvertebral and hip fractures (Cummings NEJM 2009). It is associated with greater gains in bone mineral density (BMD) and decreases in bone turnover markers than alendronate, in both treatment-naïve subjects and those previously treated with alendronate (Brown JBMR 2009; Kendler JBMR 2010). Objectives To compare the efficacy and safety of DMAb and risedronate (RIS) over 12 months in postmenopausal women considered suboptimally adherent to prior daily or weekly alendronate therapy. Methods This study randomised postmenopausal women aged ≥55 years to open-label DMAb 60 mg SC Q6M or open-label RIS 150 mg PO QM for 12 months. Primary endpoint: % change from baseline in total hip (TH) BMD at month 12. Other endpoints: % change from baseline in femoral neck (FN) and lumbar spine (LS) BMD at month 12; % change from baseline in serum CTX at months 1 and 6; and safety. Results In 870 subjects (435 DMAb, 435 RIS), mean (SD) age was 68 (7) years, mean (SD) BMD T-scores at TH, FN and LS were –1.6 (0.9), –1.9 (0.7) and –2.2 (1.2), respectively, and median CTX was 0.3 ng/mL. DMAb significantly increased mean (95% confidence interval) BMD from baseline to month 12 compared with RIS at TH [2.0% (1.8%, 2.3%) vs 0.5% (0.2%, 0.7%), respectively], FN [1.4% (1.0%, 1.7%) vs 0% (-0.4%, 0.3%)] and LS [3.4% (3.1%, 3.8%) vs 1.1% (0.7%, 1.5%); all p<0.0001]. DMAb significantly decreased CTX compared with RIS at month 1 (median change from baseline: –78% vs –17%) and month 6 (–61% vs –23%; both p<0.0001). Overall adverse events (AEs) and serious AEs were similar between groups. Conclusions In postmenopausal women suboptimally adherent to alendronate treatment, switching to DMAb was more effective than to RIS, based on significantly greater increases in BMD at all measured sites and greater reductions in CTX with DMAb. Acknowledgements This study and abstract were sponsored by Amgen and GSK. Disclosure of Interest C. Roux Grant/research support from: Amgen, Bongrain, MSD, Consultant for: Amgen, Lilly, MSD, Novartis, Roche, A. Fahrleitner-Pammer: None Declared, P. Ho Shareholder of: Amgen, Employee of: Amgen, F. Hawkins: None Declared, L. Hofbauer: None Declared, M. Micaelo: None Declared, S. Minisola Consultant for: Amgen, Bruno Farmaceutici, Eli Lilly, Merck Sharp & Dohme, Pfizer, Sigma Tau, Stroder, Speakers bureau: Abiogen, Amgen., Bruno Farmaceutici, Merck Sharp & Dohme, Nycomed, Novartis, Pfizer, Sigma Tau, N. Papaioannou Grant/research support from: Eli Lilly, Amgen, Consultant for: Amgen, Speakers bureau: Eli Lilly, Amgen, Servier, M. Stone: None Declared, J. Wark: None Declared, M. Zillikens: None Declared, I. Ferreira Shareholder of: Bristol Myers-Squibb, Novartis and Amgen, Employee of: Amgen, S. Siddhanti: None Declared, R. Wagman Shareholder of: Amgen, Employee of: Amgen, J. Brown Grant/research support from: Amgen, Eli Lilly, Merck, Novartis, Pfizer, Servier, Roche, Takeda, Warner Chilcott, Consultant for: Amgen, Eli Lilly, Merck, Speakers bureau: Amgen, Eli Lilly, Merck

Low-cost air quality sensors offer significant potential for enhancing urban air quality networks by providing higher-spatiotemporal-resolution data needed, for example, for evaluation of air quality interventions. However, these sensors present methodological and deployment challenges which have historically limited operational ability. These include variability in performance characteristics and sensitivity to environmental conditions. In this work, we investigate field “baselining” and interference correction using random forest regression methods for low-cost sensing of NO2, PM10 (particulate matter) and PM2.5. Model performance is explored using data obtained over a 7-month period by real-world field sensor deployment alongside reference method instrumentation. Workflows and processes developed are shown to be effective in normalising variable sensor baseline offsets and reducing uncertainty in sensor response arising from environmental interferences. We demonstrate improvements of between 37 % and 94 % in the mean absolute error term of fully corrected sensor datasets; this is equivalent to performance within ±2.6 ppb of the reference method for NO2, ±4.4 µg m−3 for PM10 and ±2.7 µg m−3 for PM2.5. Expanded-uncertainty estimates for PM10 and PM2.5 correction models are shown to meet performance criteria recommended by European air quality legislation, whilst that of the NO2 correction model was found to be narrowly (∼5 %) outside of its acceptance envelope. Expanded-uncertainty estimates for corrected sensor datasets not used in model training were 29 %, 21 % and 27 % for NO2, PM10 and PM2.5 respectively.