Evaluation of minimal fracture liaison service resource : costs and survival in secondary fracture prevention-a prospective one-year study in South-Finland

Background Fracture liaison service (FLS) is a secondary prevention model for identification of patients at risk for fragility fractures. Aims This study was conducted to evaluate the number and costs of secondary prevention of low-energy fractures in the city of Kouvola in Finland. Methods Women aged >= 45 years and men >= 60 years treated in the emergency department with a low-energy fracture were identified. Laboratory testing, BMI, and DXA scans were performed. Fracture Risk Assessment Tool was used. The direct FLS costs were calculated. Survival was analyzed using univariate and multivariate analysis and the life-table method. Results 525 patients with 570 fractures were identified. The mean age of women was 73.8 years and of men 75.9 years. Most patients sustained wrist (31%), hip (21%) or proximal humerus (12%) fractures. 41.5% of the patients had osteoporosis according to DXA scans. 62% of patients used calcium and vitamin D daily and 38% started anti-osteoporotic medication. Protective factors for survival were: age <80 years, female sex, and S-25OHD concentration of 50-119 nmol/L. Excess mortality was highest among patients with a fracture of the femur. The total annual direct costs of FLS were 1.3% of the costs of all fractures. Discussion Many low-energy fracture types were associated with excess mortality. The use of anti-osteoporotic medication was not optimal. Conclusions FLS increased the catchment of low-energy fracture patients and was inexpensive. However, identification, evaluation and post-fracture assessment of patients should be expedited. Rehabilitation of hip fracture patients needs to be improved.Peer reviewe

Steroid-free medium discloses oestrogenic effects of the bisphosphonate clodronate on breast cancer cells

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prediction of Drug-Drug Interactions Arising from CYP3A induction Using a Physiologically Based Dynamic Model

Using physiologically based pharmacokinetic modeling, we predicted the magnitude of drug-drug interactions (DDIs) for studies with rifampicin and seven CYP3A4 probe substrates administered i.v. (10 studies) or orally (19 studies). The results showed a tendency to underpredict the DDI magnitude when the victim drug was administered orally. Possible sources of inaccuracy were investigated systematically to determine the most appropriate model refinement. When the maximal fold induction (Ind(max)) for rifampicin was increased (from 8 to 16) in both the liver and the gut, or when the Ind(max) was increased in the gut but not in liver, there was a decrease in bias and increased precision compared with the base model (Ind(max) = 8) [geometric mean fold error (GMFE) 2.12 vs. 1.48 and 1.77, respectively]. Induction parameters (mRNA and activity), determined for rifampicin, carbamazepine, phenytoin, and phenobarbital in hepatocytes from four donors, were then used to evaluate use of the refined rifampicin model for calibration. Calibration of mRNA and activity data for other inducers using the refined rifampicin model led to more accurate DDI predictions compared with the initial model (activity GMFE 1.49 vs. 1.68; mRNA GMFE 1.35 vs. 1.46), suggesting that robust in vivo reference values can be used to overcome interdonor and laboratory-to-laboratory variability. Use of uncalibrated data also performed well (GMFE 1.39 and 1.44 for activity and mRNA). As a result of experimental variability (i.e., in donors and protocols), it is prudent to fully characterize in vitro induction with prototypical inducers to give an understanding of how that particular system extrapolates to the in vivo situation when using an uncalibrated approach