Pretreatment levels of bone turnover and the antifracture efficacy of alendronate: The fracture intervention trial

Introduction: Previous trials have shown that high bone turnover is associated with greater increases in BMD among bisphosphonate-treated women. The influence of pretreatment bone turnover levels on antifracture efficacy has not been well studied. Materials and Methods: We randomized women 55-80 years of age with femoral neck BMD T scores -2.5 and no prevalent vertebral fracture). Pretreatment levels of bone-specific alkaline phosphatase (BSALP), N-terminal propeptide of type I collagen (PINP), and C-terminal cross-linked telopeptide of type 1 collagen (sCTx) were measured in all participants using archived serum (20% fasting). The risk of incident spine and nonspine fracture was compared in ALN- and PBO-treated subjects stratified into tertiles of baseline bone marker level. Results and Conclusions: During a mean follow-up of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were documented. Compared with placebo, the reduction in nonspine fractures with ALN treatment differed significantly among those with low, intermediate, and high pretreatment levels of PINP levels (p = 0.03 for trend). For example, among osteoporotic women in the lowest tertile of pretreatment PINP ( 56.8 ng/ml). Results were similar among women without osteoporosis at baseline. Although they did not reach statistical significance, similar trends were observed with baseline levels of BSALP. Conversely, spine fracture treatment efficacy among osteoporotic women did not differ significantly according to pretreatment marker levels. Spine fracture treatment efficacy among nonosteoporotic women was related to baseline BSALP (P = 0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater among both osteoporotic and nonosteoporotic women with high pretreatment,,PINP. If confirmed in other studies, these findings suggest that bisphosphonate treatment may be most effective in women with elevated bone turnover

Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: the FLEX study.

ImportanceDiscontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established.ObjectiveTo test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years.Design, setting, and participantsThe prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group. Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at FLEX baseline and after 1 and 3 years.Main outcomes and measuresSymptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover.ResultsDuring 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year. One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]).Conclusions and relevanceAmong postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended.Trial registrationclinicaltrials.gov Identifier: NCT00398931

The global contribution of forage fish to marine fisheries and ecosystems

Forage fish play a pivotal role in marine ecosystems and economies worldwide by sustaining many predators and fisheries directly and indirectly. We estimate global forage fish contributions to marine ecosystems through a synthesis of 72 published Ecopath models from around the world. Three distinct contributions of forage fish were examined: (i) the ecological support service of forage fish to predators in marine ecosystems, (ii) the total catch and value of forage fisheries and (iii) the support service of forage fish to the catch and value of other commercially targeted predators. Forage fish use and value varied and exhibited patterns across latitudes and ecosystem types. Forage fish supported many kinds of predators, including fish, seabirds, marine mammals and squid. Overall, forage fish contribute a total of about $16.9 billion USD to global fisheries values annually, i.e. 20$5.6 billion, fisheries supported by forage fish were more than twice as valuable ($11.3 billion). These estimates provide important information for evaluating the trade-offs of various uses of forage fish across ecosystem types, latitudes and globally. We did not estimate a monetary value for supportive contributions of forage fish to recreational fisheries or to uses unrelated to fisheries, and thus the estimates of economic value reported herein understate the global value of forage fishes.</p

The global contribution of forage fish to marine fisheries and ecosystems

Forage fish play a pivotal role in marine ecosystems and economies worldwide by sustaining many predators and fisheries directly and indirectly. We estimate global forage fish contributions to marine ecosystems through a synthesis of 72 published Ecopath models from around the world. Three distinct contributions of forage fish were examined: (i) the ecological support service of forage fish to predators in marine ecosystems, (ii) the total catch and value of forage fisheries and (iii) the support service of forage fish to the catch and value of other commercially targeted predators. Forage fish use and value varied and exhibited patterns across latitudes and ecosystem types. Forage fish supported many kinds of predators, including fish, seabirds, marine mammals and squid. Overall, forage fish contribute a total of about $16.9 billion USD to global fisheries values annually, i.e. 20$5.6 billion, fisheries supported by forage fish were more than twice as valuable ($11.3 billion). These estimates provide important information for evaluating the trade-offs of various uses of forage fish across ecosystem types, latitudes and globally. We did not estimate a monetary value for supportive contributions of forage fish to recreational fisheries or to uses unrelated to fisheries, and thus the estimates of economic value reported herein understate the global value of forage fishes.</p

The global contribution of forage fish to marine fisheries and ecosystems. Fish and Fisheries

Abstract Forage fish play a pivotal role in marine ecosystems and economies worldwide by sustaining many predators and fisheries directly and indirectly. We estimate global forage fish contributions to marine ecosystems through a synthesis of 72 published Ecopath models from around the world. Three distinct contributions of forage fish were examined: (i) the ecological support service of forage fish to predators in marine ecosystems, (ii) the total catch and value of forage fisheries and (iii) the support service of forage fish to the catch and value of other commercially targeted predators. Forage fish use and value varied and exhibited patterns across latitudes and ecosystem types. Forage fish supported many kinds of predators, including fish, seabirds, marine mammals and squid. Overall, forage fish contribute a total of about $16.9 billion USD to global fisheries values annually, i.e. 20$5.6 billion, fisheries supported by forage fish were more than twice as valuable ($11.3 billion). These estimates provide important information for evaluating the trade-offs of various uses of forage fish across ecosystem types, latitudes and globally. We did not estimate a monetary value for supportive contributions of forage fish to recreational fisheries or to uses unrelated to fisheries, and thus the estimates of economic value reported herein understate the global value of forage fishes

The global contribution of forage fish to marine fisheries and ecosystems. Fish and Fisheries

Abstract Forage fish play a pivotal role in marine ecosystems and economies worldwide by sustaining many predators and fisheries directly and indirectly. We estimate global forage fish contributions to marine ecosystems through a synthesis of 72 published Ecopath models from around the world. Three distinct contributions of forage fish were examined: (i) the ecological support service of forage fish to predators in marine ecosystems, (ii) the total catch and value of forage fisheries and (iii) the support service of forage fish to the catch and value of other commercially targeted predators. Forage fish use and value varied and exhibited patterns across latitudes and ecosystem types. Forage fish supported many kinds of predators, including fish, seabirds, marine mammals and squid. Overall, forage fish contribute a total of about $16.9 billion USD to global fisheries values annually, i.e. 20$5.6 billion, fisheries supported by forage fish were more than twice as valuable ($11.3 billion). These estimates provide important information for evaluating the trade-offs of various uses of forage fish across ecosystem types, latitudes and globally. We did not estimate a monetary value for supportive contributions of forage fish to recreational fisheries or to uses unrelated to fisheries, and thus the estimates of economic value reported herein understate the global value of forage fishes