From Replicative Senescence to Microrna Based Diagnostics of Age-Associated Diseases

Abstract

BMD is most often described as a T-score or Z-score, both of which are units of standard deviation (SD). The Z-score describes the number of SDs by which the BMD in an individual differs from the mean value expected for age and sex. The T-score describes the number of SDs by which the BMD in an individual differs from the mean value expected in young healthy individuals.The operational defi nition of osteoporosis is based on the T-score for BMD assessed at the femoral neck and is defi ned as a value for BMD 2.5 SD or more below the young female adult mean (T-score less than or equal to -2.5 SD).The recommended reference range for calculating the T-score is the NHANES III reference database for femoral neck measurements in women aged 20-29 years. Note that the diagnostic criteria for men use the same female reference range as that for women. This arises fortuitously because for any age and BMD at the femoral neck, the risk of hip fracture or a major osteoporotic fracture is about the same in men and women. However, the T-score cannot be used interchangeably with different techniques and at different sites, since the prevalence of osteoporosis and proportion of individuals allocated to any diagnostic category would vary, as does the risk of fracture.Because a variety of non-skeletal factors contributes to fracture risk, the diagnosis of osteoporosis by the use of BMD measurements is at the same time an assessment of a risk factor for the clinical outcome of fracture. For these reasons there is a distinction to be made between the use of BMD for diagnosis and for risk assessment. Since BMD forms but one component of fracture risk, accurate assessment of fracture risk should take into account other readily measured indices of fracture risk that add information to that provided by BMD.A large number of additional risk factors for fracture have been identifi ed. For the purposes of risk assessment, interest lies in those factors that contribute signifi cantly to fracture risk over and above that provided by bone mineral density measurements or age. A caveat is that some risk factors are not amenable to particular treatments, so that the relationship between absolute probability of fracture and reversible risk is important. Liability to falls is an appropriate example where the risk of fracture is high, but treatment with agents affecting bone metabolism may (arguably) have little effect on risk.The FRAX algorithms, developed by the WHO Collaborating Centre for Metabolic Bone Diseases at Sheffi eld, integrate the weight of clinical risk factors for fracture risk, with or without information on BMD, and have been developed by the WHO Collaborating Centre for Metabolic Bone Diseases at Sheffi eld, UK. The risk factors comprise age, sex, low body mass index, previous fragility fracture, parental history of hip fracture, glucocorticoid treatment, current smoking, alcohol intake 3 or more units daily, rheumatoid arthritis and other secondary causes of osteoporosis. The output of FRAX is the 10-year probability of a major os...