the potential clinical impact—appraisal of the precision, size and clinical importance or relevance of the primary outcomes used to determine the safety and effectiveness of the test; the generalisability of the evidence to the target population; and the applicability of the evidence—integration of the evidence for conclusions about the net clinical benefit of the intervention in the context of Australian clinical practice. A matrix for assessing the body of evidence for each research question, according to the components above, was used for this assessment (Table 14). Table 14 Body of evidence matrix Component A B C D Excellent Good Satisfactory Poor Evidence-base a One or more level I studies with a low risk of bias or several level II studies with a low risk of bias One or two level II studies with a low risk of bias, or an SR or several level III studies with a low risk of bias One or two level III studies with a low risk of bias, or level I or II studies with a moderate risk of bias Level IV studies, or level I to III studies/SRs with a high risk of bias Consistency b All studies consistent Most studies consistent and inconsistency may be explained Some inconsistency reflecting genuine uncertainty around clinical question Evidence is inconsistent Clinical impact Very Substantial Moderate Slight or restricted Generalisability Population(s) studied in body of evidence are the same as target population Population(s) studied in the body of evidence are similar to target population Population(s) studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population c Population(s) studied in body of evidence differ from target population and hard it is to judge whether it is sensible to generalise to target population Applicability Directly applicable to Australian healthcare context Applicable to Australian healthcare context with few caveats Probably applicable to Australian healthcare context with some caveats Not applicable to Australian healthcare context Source: adapted from ) a Level of evidence determined from the NHMRC evidence hierarchy (see Table 12) b If there is only one study, rank this component as ‘not applicable’ c For example, results in adults that are clinically sensible to apply to children OR psychosocial outcomes for one cancer that may be applicable to patients with another cancer SR = systematic review; several = more than two studies
are the harms associated with osteoporosis screening?’ Screening included BMD measurements and mainly involved DXA testing. Unfortunately, no studies were identified in this systematic review that evaluated the potential harms from screening. The lack of empirical evidence in this high-quality systematic review on safety confirmed that we had not missed any relevant studies in our literature searches. Is it effective? Direct evidence of diagnostic effectiveness Does BMD analysis using DXA for women in their 50th year improve health outcomes? Summary—For in their 50th year, what is the effectiveness of using DXA to diagnose low or low–normal BMD, compared with clinical assessment (including the use of existing fracture risk assessment tools but no DXA) of the risk of low BMD, in order to prevent minimal trauma fracture? No studies were that met all the inclusion criteria. A systematic review (Nelson et al. 2010) asking a similar research question identified no trials on the effectiveness of DXA screening. A further two studies that also had similar research questions were included and are described below due to the lack of evidence. In both these studies there was no information on the specified outcomes of fracture risk, quality of life or mortality/morbidity. The two studies measured change in BMD 1–2 years after a DXA test. Gutin et al. (1992) reported that the expected age-related reduction in BMD between visits was not found 12–18 months after DXA and subsequent lifestyle counselling in postmenopausal women. Winzenberg et al. (2006) reported a 1.1% increase per year (95%CI +0.9, +1.4) in femoral neck BMD from baseline to 2 years, and no change in lumbar spine BMD (+0.09% p.a.; 95%CI –0.06, +0.20) in premenopausal women. They concluded that DXA testing plus providing BMD results and lifestyle information is effective at increasing hip BMD during a 2-year follow-up. Studies would have been included to assess the effectiveness of DXA testing of women in their 50th year if they had met the criteria outlined a priori in Box 2. Box 2 Criteria for selecting studies to assess the effectiveness of BMD analyses using DXA on fracture risk, quality of life and morbidity/mortality in women in their 50th year Selection criteria Inclusion criteria
Seven municipalities in Japan; baseline 1996 recruited from the community into the Japanese Population-based Osteoporosis Cohort Study; followed up at 10 years after baseline; response rate 84.7% Low risk of bias in of population selection and study design; however, high risk of bias in terms of coverage of fractures as only self-reports included, and follow up not good Limited population applicability Mean age 56.7±9.6 years Fractures based on Surveys undertaken in 1999, 2002 and 2006; first fracture counted as end of follow-up time register; no other inclusion criteria described Excluded from the analysis were women without baseline DXA and women who were taking HRT or osteoporosis drugs at baseline nurse interview but no independent verification DXA = dual X-ray absorptiometry; FRAX® = WHO Fracture Risk Calculator Table 40 Studies included to determine whether proposed DXA testing would result in a change in management: exercise Study Study design / Quality appraisal Study population Selection criteria Studies included Findings Moayyeri () Systematic review of exercise interventions for preventing fracture No systematic quality appraisal of studies reported; other parts of review satisfactory; overall unclear risk of bias Men and (reported separately) older than 40 years of age (although some studies included younger participants) Systematic reviews, RCTs and prospective studies featuring a measure of exercise with fracture as an outcome Studies with participants all under 40 years of age and not in English were excluded No RCTs found; 21 prospective studies fulfilled the inclusion criteria Studies with hip fracture as an endpoint were pooled in other studies not suitable Included studies were all quite large (between 1,959 and 93,676 participants), ages 35 years and older; duration of follow-up between 4 and 15 years Exercise variously categorised as walking and moderate, regular and intermediate work activity Exercise protective against hip fracture in women (RR 0.62; 95%CI 0.56, 0.69) Low heterogeneity Association likely to be confounded by other health-related issues such as Problems associated with low event rates in these studies Data for other fracture sites variable; limited evidence for protective impact of exercise on vertebral fractures; possible increases in risk of wrist and other site fractures with exercise
Research and Quality review interventions (current to March 2011) Low risk of bias One pooled analysis found a statistically significant increased risk of hip fracture, but another with many more participants found a significant reduction in hip fracture One review of 9 studies found statistically significant risk reduction for calcium, greater with higher dose of calcium Cumming & Nevitt () Systematic review to assess the effectiveness of calcium supplements and/or dietary calcium for the prevention of fractures in postmenopausal women Quality appraisal and risk of bias was not reported, unclear risk of bias No restrictions on population described Studies had to have fracture as an outcome Ecologic studies were excluded Four RCTs of calcium supplements (mean age of participants was older than 70 years in 3 studies, and 58 years in 4th); 3 trials of calcium supplements (mean age years); 7 observational epidemiologic studies of calcium supplements; and 23 observational epidemiologic studies of dietary calcium (18 concerned with hip fractures) In RCTs number of subjects in each study were 78, 93, 197 and 3,270 Follow-up was 1.5–4.3 The main finding was that increased calcium intake postmenopausal women appears to be associated with a small reduction in risk of fracture Conclusion is based on consistent findings of RCTs and a meta-analysis of 16 observational epidemiologic studies of dietary calcium and hip fractures National Osteoporosis Foundation () Systematic review of interventions for preventing fracture; covers many interventions Quality appraisal not reported Unclear risk of bias No restrictions on population described RCTs with a calcium supplementation intervention, and with fracture as an outcome Four RCTs with oral calcium supplementation, mean age of participants was than 70 years in 3 studies, and 58.5 years in 4th; 1 study had men and women, whereas the rest had women only; mix of participants with and without previous fractures; follow-up Widely varying results due to differences in populations, treatments and sample sizes; while each study suggests an effect in reducing fracture probabilities, range of uncertainty is too wide to make a definitive statement about magnitude of effect