Fracture Outcome

Raloxifene combined with alendronate produced greater BMD effects than raloxifene alone, but not greater than alendronate alone. The impact on fracture outcomes, however, is not yet known. Contrary to bisphosphonate discontinuation—in which the achieved BMD is maintained or decreased much more slowly than among those in the placebo group—raloxifene discontinuation results in BMD decreasing immediately at a rate similar to that of placebo. ... 

Siris ES, Miller PD, Barrett-Connor E, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women Results from the National Osteoporosis Risk Assessment. JAMA 2001 286 2815-2222. 

Figures, Typical fracture outcome. The specimen strip was sandwiched between gla.ss slides. One glass slide was removed after a test to allow the harvesting of the fragments. This image shows the front glass slide partially slid downwards to expose the fragments.

Raloxifene increases bone mineral density and reduces fracture rates. In trials of 1 to 3 years, raloxifene increased vertebral and hip bone mineral density by 2% to 3% and 1% to 2%, respectively.30 32 In the Multiple Outcomes for Raloxifene Evaluation (MORE) trial, raloxifene decreased the risk of vertebral fractures by 30% in postmenopausal with at least one prior fracture.30 No significant reduction in nonvertebral fractures was reported. 

Prior to installing a new shutdown system, however, a fault tree analysis was performed on the proposed modifications. From this study, it was concluded that the overall frequency of brittle fracture was lowered from 5x10"4 to 5 x 10-5 (occurrences/year). Using this new frequency in the calculation for aggregate risk would result in revised outcome frequencies and F-N data points, as shown below. 

Vertebral fracture as outcome denotes risk reduction during fourth year of treatment... 

Delmas PD, Ensrud KE, Adachi JD, Harper KD, Sarkar S, Gennari C, Reginster JY, Pols HAP, Recker RR, Harris ST, Wu W, Genant HK, Black DM, Eastell R for the Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators (2002) Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis four-year results from a randomized clinical trial. J Clin Endocrinol Metab 87 3609-3617... 

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. J Am Med Assoc 282 637-645... 

Kanis JA, Johnell O, Black DM, Downs RW Jr, Sarkar S, Fuerst T, et al. (2003) Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial. Bone 33 293-300... 

Siris ES, Harris ST, Eastell R, Zanchetta J, Goemaere S, Diez-Perez A et al (2004) Effect of raloxifene on the risk of nonvertebral fractures after 8 years results from the Continuous Outcomes Relevant to Evista (CORE) study. J Bone Miner Res 19(Suppl 1) F428... 

New SERMS are in different development stages. Lasoftmfene has been shown to have positive effects on bone and lipid metabolism without negative impact on uterine growth (Ke et al. 1998). There is a large-sample, prospective, randomized clinical trial in progress in which breast cancer, together with fracture prevention, is one of the main outcomes. 

Colledge NR, Wilson 1A, Macintyre CC et al. (1994) The prevalence and characteristics of dizziness in an elderly community. Age Ageing 23(2) 117-120 The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. (1996) Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology 46(5) 1470 Cooper C, Atkinson El, lacobsen SI et al. (1993) Population-based study of survival after osteoporotic fractures. Am 1 Epidemiol 137(9) 1001-1005 Cummings SR and Melton LI (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359(9319) 1761-1767... 

While biochemical markers of bone metabolism may be sensitive to the effects of glucocorticoids in the short term, the relation between changes in these markers and intermediate measures, such as bone mineral density, and the more important clinical outcomes of fractures, is unknown. In a random stratified sample of 3222 women in the perimenopausal age range (47-56 years), including 119 women with asthma, bone mineral density was measured to determine whether asthma was a risk factor of osteoporosis and to investigate the effect of inhaled glucocorticoids (102). The subjects had predominantly adult-onset asthma, as the age at diagnosis was over 40 years. There were 26 patients who were treated mainly with... 

Estimates of the important outcome of bone fracture have shown a small increased risk with inhaled glucocorticoids, but this may well be a feature of the disease rather than the therapy, because comparisons with treatment with bronchodilator drugs show no difference between risk factors in patients taking glucocorticoids or bronchodilators. 

Continued treatment with bisphosphonate may also be appropriate to not only reduce the likelihood of recurrent hypercalcaemia but also to manage Mrs CR s bone metastases. Many guidelines (including the NICE Improving outcomes guidance for breast cancer, 2002a) recommend the use of bisphos-phonates to reduce the onset of skeletal complications such as skeletal fractures. An appropriate suggestion would be to continue one of the bisphosphonates previously outlined at three-weekly intervals (to coincide with chemotherapy administration). 

Fracture is the only important outcome of osteoporosis and the evidence to support the efficacy of various interventions appears in Table 38.2. 

Thus, whether a crack will run a great distance or quickly arrest depends on the relative rates of crack propagation and depressurization. Prediction of the outcome requires a computer code that compares the gas dynamics and the fracture dynamics. The framework for such RCP prediction has been developed [1], but an important task remains before RCP management can be implemented A ftindamentally sound, independent test for measuring the material property governing RCP and crack arrest. 

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