J A Kanis

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..The combination of clinical risk factors and BMD provide higher specificity and sensitivity than either alone. INTRODUCTION AND HYPOTHESES: To develop a risk assessment tool based on clinical risk factors (CRFs) with and without BMD...

..It has been suggested that bone mineral density (BMD) measurements should be made at multiple sites, and that the lowest T-score should be taken for the purpose of diagnosing osteoporosis...

..In relation to threshold values that are recommended in the UK, the analysis suggests that raloxifene is cost-effective in the treatment of postmenopausal women at an increased risk of vertebral fractures...

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..The total direct costs were estimated at 31.7 billion Euros (21.165 billion UK pounds), which were expected to increase to 76.7 billion Euros (51.1 billion UK pounds) in 2050 based on the expected changes in the demography of Europe...

..We conclude that reported intake of alcohol confers a risk of some importance beyond that explained by BMD. The validation of this risk factor on an international basis permits its use in case-finding strategies...

..Its validation on an international basis permits the use of this risk factor in case finding strategies...

..5 SD) but without a prior vertebral fracture, treatment exceeded the threshold for cost-effectiveness. However, if an additional, independent risk factor was assumed (e.g., corticosteroid use) treatment became cost-effective...

..Its validation on an international basis permits the use of this risk factor in case finding strategies...

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..The use of absolute risk permits information from different types of bone mineral measurements to be applied for the assessment of patients, either alone or in combination with other independent risk factors...

..Assessment and intervention thresholds are developed and proposed in men aged over 50 years and postmenopausal women for the UK based on fracture probability from the WHO fracture risk assessment tool (FRAX)...

..A relatively simple adjustment of conventional FRAX estimates of probabilities of hip fracture and a major osteoporotic fracture can be applied to modulate the risk assessment with knowledge of the dose of glucocorticoids...

..There was no significant effect on non-vertebral fracture...

..The FRAX tool integrates information on fracture risk from clinical risk factors with or without the use of BMD and can be used to improve the targeting of individuals at high fracture risk...

..This review highlights a number of avenues for further research, such as improved definition of thresholds of compliance and persistence, as well as gap length, offset times, and fraction of benefit...

..The tool increases sensitivity without trading specificity and is now being used in the re-appraisal of clinical guidelines...

..With the revised tool, there were strong correlations (r > 0.99) between versions 2.0 and 3.0 for FRAX estimates of fracture probability, but the revised models gave lower probability estimates...

..Hazard ratios for the effect of strontium ranelate on the fracture outcome did not change significantly with increasing fracture probability...

..The tool increases sensitivity without trading specificity, and is now being used in the reappraisal of clinical guidelines...

..No significant effect was noted on the risk of clinical fractures, but fracture risk reduction was reported in a post hoc subgroup analysis in a high risk group categorised on the basis of BMD and prior fracture...

..The consensus views on osteoporosis in men are reported...

..A fracture risk assessment tool (FRAX) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK...

..Guidance is provided in a European setting on the assessment and treatment of postmenopausal women with or at risk from osteoporosis...

..Its identification on an international basis supports the use of this risk factor in case-finding strategies...

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..This study demonstrates that the estimation of an individual's 10-year probability of fracture by the FRAX algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy...

..Intervention thresholds based on hip BMD T-scores are similar between sexes...

..We conclude that segments of the apparently healthy population could be advantaged by treatment if efficacy were supported by randomized controlled studies...

..We conclude that vertebral fractures have a major personal and societal impact that needs to be recognised in algorithms for assessment of risk and in health economic strategies for osteoporosis...

..Fall risk does not significantly impact on the efficacy of the bisphosphonate clodronate in reducing the incidence of fracture...

..Although data are limited, prior fragility fractures increase subsequent fracture risks in both men and women. These studies suggest that the same BMD criteria used to diagnose osteoporosis in women can be applied to men...

..3-9.9], and 20-fold higher in women with soft-tissue metastases without evidence of skeletal metastases (OR, 22.7; 95% CI, 9.1-57.1). We conclude that vertebral fracture risk is markedly increased in women with breast cancer...

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..Recent studies have evaluated the performance of FRAX® in independent cohorts. The interpretation of most is problematic for reasons summarised in this perspective...

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..Hip fracture was a more common cause for mortality than pancreatic or stomach cancer. Thus, interventions that decreased hip fracture rate by, say, 50% would avoid 0.75% or more of all deaths...

..The decrease in relative risk with age is, however, associated with an increase in absolute risk. Thus, for clinical use, the expression of absolute risks may be preferred to relative risks...

..We conclude that clodronate 800 mg daily is effective in preventing bone loss, and at 1 year, there is a trend consistent with antifracture efficacy in patients with established osteoporosis regardless of causation...

..Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review..

..There was a greater than 10-fold variation in hip fracture risk and fracture probability between countries...

..The competitive price of generic bisphosphonates has had a marked effect on practice guidelines, but an increasing body of evidence suggests that they have more limited effectiveness than generally assumed...

..0/SD). Such gradients might be achieved with the use of multiple risk factors to identify patients at risk...

..To determine whether strategies can be devised for the assessment and treatment of glucocorticoid-induced osteoporosis (GIO)...

..A country-specific FRAX® model was developed from the epidemiology of fracture and death in Belgium. Fracture probabilities were identified that corresponded to currently accepted reimbursement thresholds...

..If the age-specific incidence of hip fracture continues, the number of hip fractures would increase by a further 46%...

..These observations, however, require confirmation in prospective clinical trials...

..If fracture studies are required by regulatory agencies, there is still a requirement for placebo-controlled studies, although perhaps of shorter duration than demanded at present...

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..We conclude that both agents are effective in the management of hypercalcaemia of malignancy. At the doses studied, the effects of pamidronate are more complete and longer lasting than those of clodronate...

..This figure rose to 23 per 1000 at the age of 70 years. We conclude that, although uncertainty exists concerning the offset of effect of treatments, treatments should be optimally given to women without prior fractures in later life...

..Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk of fractures due to osteoporosis...

..It is not known whether more potent bisphosphonates will deliver greater clinical efficacy in the future...

..Criteria like loss of height and/or spine curvature perform relatively poorly, reflecting the need for further investigation to better identify those needing BMD assessment...

..In this review we argue that, if new agents are to be developed, there is still a place for the placebo-controlled trial. A move to studies of equivalence or non-inferiority raises more problems than it resolves...

..The impact of BMD, age and other risks on fracture probability have recently been determined and provide a mechanism for optimising assessment of patients so that treatments can be efficiently directed to those most in need...

..We conclude that aminohexane bisphosphonate is an effective agent in the treatment of tumour-induced hypercalcaemia, with rapid onset of effect and low toxicity...

..Given, however, the unchanging survival in patients with metastatic bone disease, significant improvements in the quality of remaining life is an important therapeutic effect...

..The single infusion has a more rapid onset of effect, is more convenient than multiple infusions, and has no adverse effect on renal function...

..We report unusual clinical and radiological features of Paget's disease of bone in three family members. All three patients had satisfactory biochemical and symptomatic response to treatment with an intravenous bisphosphonate (clodronate)...