2007防治炎性肠病骨质疏松指南

BRITISH SOCIETY OF GASTROENTEROLOGY Guidelines for osteoporosis in inflammatory bowel disease and coeliac disease Written and approved by the British Society of Gastroenterology June 2007 http://www.bsg.org.uk Designed, Typeset and Printed by Q3 Digital/Litho Loughborough, Leicestershire 01509 213456 14 CONTENTS 1.0 The Problem 2.0 Risk factors for fracture in general 2.1 Reduced bone mineral density 2.1.1 The importance of low BMD 2.1.2 Measurement of BMD 2.1.3 Risk factors for low BMD and fracture 2.2 Other risk factors for fracture independent of low BMD 3.0 Osteoporosis in IBD 3.1 Are fractures a problem in IBD? 3.2 Risk factors for fracture in IBD 3.2.1 Reduced BMD 3.2.2 Factors affecting BMD in IBD 3.2.2.1 Age and age at diagnosis 3.2.2.2 Gender 3.2.2.3 Weight, height and body mass index3.2.2.4 Duration of disease 3.2.2.5 Disease site, activity, severity and previous surgery 3.2.2.6 Corticosteroid use 3.2.2.7 Reduced physical activity 3.2.2.8 Smoking 3.2.3 Other risk factors for fracture independent of low BMD 3.2.3.1 Age 3.2.3.2 Gender 3.2.3.3 Corticosteroid use and disease activity 4.0 Osteoporosis in coeliac disease 4.1 Are fractures a problem in coeliac disease? 4.2 Risk factors for fracture in coeliac disease 4.2.1 Reduced BMD 4.2.2 Factors affecting low BMD in coeliac disease 4.2.2.1 Years exposed to gluten 4.2.2.2 Gender 4.2.2.3 Body mass index (BMI) 4.2.2.4 Degree of villous atrophy 4.2.2.5 Symptomatic disease 4.2.2.6 Adherence to a gluten-free diet 5.0 Prevention of osteoporosis in IBD and coeliac disease 5.1 General measures 5.2 Calcium 5.3 Vitamin D 5.4 Steroid avoidance in IBD 5.5 Bone-protective measures during steroid use in IBD 6.0 Detection of osteoporosis in IBD and coeliac disease 6.1 Indications for DEXA 6.2 Special considerations in IBD 6.2.1 DEXA in steroid treated patients 6.3 Special considerations in coeliac disease 7.0 Treatment of osteoporosis 7.1 Bisphosphonates 7.2 Teriparatide 7.3 Raloxifene 7.4 Calcitonin 7.5 Calcium and vitamin D 7.6 Strontium 7.7 Sex hormone replacement therapy (HRT) 7.8 Fluoride 8.0 Summary of recommendations 9.0 The process of guideline formulation 10.0 Targets for audit References NR Lewis, BB Scott BSG Guidelines in Gastroenterology June 2007 1.0 THE PROBLEM Osteoporosis is a major public health problem becauseof its potentially severe consequences for both thepatient and the health care system if it leads to frac- ture. It has been estimated that one in two women and one in five men older than 50 years will develop an osteoporotic frac- ture during the course of their remaining lifetime in the United States [1] and that in the United Kingdom (UK) osteoporosis causes more than 200,000 fractures per year [2, 3]. Osteoporotic fractures are associated with pain, disability and up to 30% mortality at 1 year in addition to an estimated monetary cost in the UK of more than £1 billion yearly [3–5]. Osteoporosis is likely to become even more common and costly because of the ageing population. Gastroenterologists care for groups of patients at increased risk of osteoporotic fracture, such as those with inflammatory bowel disease (IBD) and coeliac disease. These guidelines review the risks of osteoporosis and fracture in these conditions with a view to identifying subgroups of patients that would benefit from screening and interventions to prevent fractures. 2.0 RISK FACTORS FOR FRACTURE IN GENERAL Before considering IBD and coeliac disease in particular it is important to consider the risk factors for fracture in general since they are likely to operate also in those conditions. 2.1 REDUCED BONE MINERAL DENSITY 2.1.1 The importance of low BMD Although osteoporosis is just one of many factors predispos- ing to fracture, it is one of the most important and can be reliably assessed by measurement of bone mineral density (BMD). BMD can be expressed as the number of standard deviations (SD) above or below either the mean BMD for young adults (T-score) or the mean BMD for age-matched controls (Z-score).Cross-sectional and prospective population studies suggest that the risk of fracture increases by a factor of 1.4 – 2.6 for each SD decrease in bone mineral density [6]. Osteoporosis is defined as a T-score <-2.5 [3]. The significance of a given T-score in terms of absolute fracture risk will differ according to age (table 1). For example, a T-score of –2 is asso- ciated with a 9.2% probability of an osteoporotic fracture in the next ten years in non-steroid treated women aged 50 years but at 70 years this probability is twice as high [7]. 2.1.2 Measurement of BMD BMD is usually measured using dual energy x-ray absorp- tiometry (DEXA) which is relatively simple and non-invasive and has accuracy and precision (measurement error of 5–6%) [8–10]. Although DEXA instruments are calibrated against excised bone samples, methodological differences in how this calibration is performed have led to large discrepancies in patient measurements when using different machines, mak- ing comparison difficult [11]. For this reason, whenever possible, follow-up examinations should be done using the same instrument. The use of BMD measurement alone as a prognostic tool in a population-screening programme is lim- ited by both its poor discriminatory power to detect those who will fracture from those that will not and its cost if used indis- criminately [6, 12–14]. Quantitative ultrasound might be considered where DEXA is not readily available. However, it doesn’t measure BMD directly and cannot be used to diagnose osteoporosis using current definitions based on BMD. Thus the T-score thresh- olds used in these guidelines cannot be applied using results from quantitative ultrasound. Nevertheless, a low quantita- tive ultrasound measurement is an independent predictor of osteoporotic fracture in post-menopausal women and may be used as such. It is not suitable for monitoring treatment. A code of practice for the use of quantitative ultrasound can be obtained from the National Osteoporosis Society (www.nos.org.uk). 2.1.3 Risk factors for low BMD and fracture There are many predisposing factors for low BMD and frac- ture. Some are modifiable; others are not. A systematic review [15] of those risk factors for fracture which are probably related to a low BMD identified high risk factors (relative risk or odds ratio of >2) and moderate risk factors (relative risk 1–2) and they are shown in Box 1. Factors which are modifi- able are indicated. There is emerging evidence that proton pump inhibitors used long term [16] and thiazolidinedones such as rosiglitazone [17] also predispose to fractures. 2.2 OTHER RISK FACTORS FOR FRACTURE INDEPENDENT OF LOW BMD There are many other factors which predispose to fracture independently, at least partly, of any effect on BMD [18,19] as shown in Box 2. Some, such as increasing age, previous fragility fracture, low body weight, poor visual acuity and neuromuscular disorders, presumably act by predisposing to or showing a predisposition to falls. Alcohol excess is another Guidelines for osteoporosis in inflammatory bowel disease and coeliac disease 1 June 2007 BSG Guidelines in Gastroenterology Table 1: 10-year probability (%) of hip, spine, proximal humerus or distal forearm fracture in non-steroid treated individuals according to T-score at femoral neck [7]. T-score Age (years) +1 0 -1 -2 -3 -4 Women 50 2.4 3.8 5.9 9.2 14.1 21.3 60 3.2 5.1 8.2 13.0 20.2 30.6 70 4.3 7.1 11.5 18.3 28.4 42.3 80 4.6 7.7 12.7 20.5 31.8 46.4 Men 50 1.2 2.0 3.4 5.8 9.6 15.9 60 1.6 2.7 4.5 7.3 11.8 18.7 70 2.3 3.8 6.2 10.0 16.0 25.0 80 3.6 5.8 9.3 14.7 22.6 33.3 Guidelines for osteoporosis in inflammatory bowel disease and coeliac disease NR Lewis, BB Scott factor [20] which may also be partly related to falls. Corticosteroid use may also predispose to fracture independ- ent of any effect on the BMD [21–23]. This may be related to higher daily dose rather than cumulative dose [24] and a rapid decrease in fracture risk towards baseline has been shown to occur shortly after stopping steroids [25, 26]. 3.0 OSTEOPOROSIS IN IBD 3.1 ARE FRACTURES A PROBLEM IN IBD? Since fracture is the only clinically important outcome of osteoporosis, it is important to determine the impact of IBD on the risk of fracture. The results of eight studies are shown in Table 2 [27–34]. They demonstrate a modest increase in fracture risk. For all fractures the relative risk is approxi- mately 1.3 for Crohn’s disease and 1.2 for UC. The risk is slightly greater for hip fractures – 1.5 for Crohn’s disease and 1.4 for UC. Since most of the studies rely on reports of frac- ture, the prevalence of spinal fracture (and therefore all fractures) is likely to be underestimated. The only two studies to use quantitative morphometry of spinal x-rays revealed a very high prevalence of vertebral fractures. In one, the researchers selected for study just over half their Crohn’s dis- ease patients by excluding those with a lumbar T-score >-1 and found a fracture prevalence of 22% [33]. The other found lumbar spine fractures in 14% of 271 patients with ileo-caecal Crohn’s disease [34]. Several risk factors for osteoporotic frac- ture specific for IBD have been identified which may be then used to target diagnostic and therapeutic interventions most appropriately. 3.2 RISK FACTORS FOR FRACTURE IN IBD 3.2.1 Reduced BMD As explained above, low BMD is an important predictor for fracture risk, although one study of Crohn’s disease patients [34] found that the vertebral fracture rate did not correlate with the BMD. The prevalence of low BMD in Crohn’s disease and ulcerative colitis observed in cross-sectional studies is summarised in tables 3 and 4, respectively [35–62]. Pooling of the results (table 5) suggests that BMD is modestly reduced in both Crohn’s and UC with mean Z-scores being approximately -0.5 and -0.7 at the spine and hip respectively in Crohn’s dis- ease and -0.1 and -0.3 at those sites in UC. When using T-scores, pooled bone mineral density in both patients with Crohn’s disease and ulcerative colitis is within the osteopenic or osteoporotic range in over half of patients. However there are limitations with these studies. Many of the studies are small with only 8 of the 40 studies having sample sizes above 100 patients with IBD. The majority of the studies are based on observations from specialist IBD clinics and not population- based and thus the findings may not reflect the true risk. Only 7 of the studies included a control group. Overall, longitudinal changes in BMD in patients with IBD were similar to those in the general population [36, 38, 40, 44, 46, 55, 56]. Pooling of these results demonstrates -0.50% change per year in spine BMD and -1.09% change per year in femoral neck BMD in patients with Crohn’s disease. In comparison, -1.33% change per year in spine BMD and +0.26% change per year in femoral neck BMD was observed in patients with ulcerative colitis. 3.2.2 Factors affecting BMD in IBD 3.2.2.1 Age and age at diagnosis As expected, advancing age was associated with reduced BMD in most studies. However, Haugeberg et al [51] observed that Crohn’s disease patients with reduced BMD were younger than those without reduced BMD (33.6 v 41.1 years at lumbar spine, p= 0.02; 34.7 v 41.5 years at femoral neck, p= 0.04 respectively) though the patients with reduced BMD had a significantly higher cumulative steroid dose. Kuisma et al [62] also observed that patients with Crohn’s disease and osteopenia were significantly younger than those with normal BMD (33.5 years [95%CI 29.4–37.6] v 40.9 [95% CI 38.3–43.5] years, respectively) and though there were no differences in cumulative steroid doses, patients with osteopenia had suf- fered more exacerbations of their Crohn’s disease. The age at diagnosis also may also be important. Though based on small numbers, Schoon et al [50] observed a greater risk of reduced BMD in patients with Crohn’s disease aged under 18 years at diagnosis (n=12) at the lumbar spine (Z-score -1.07 v 0.12, p= 0.0001) and total body (Z-score -0.86 v –0.20, p= 0.018) in comparison to those diagnosed over 18 2 NR Lewis, BB Scott BSG Guidelines in Gastroenterology June 2007 High risk (RR>2) Non-modifiable • Older age (> 70 years) • Prior osteoporotic fracture Modifiable • Low body weight (BMI <20 – 25 kg/m2 or weight <40 kg) • Weight loss (greater than 10%) • Physical inactivity • Use of corticosteroids • Use of anticonvulsants Moderate risk (RR 1-2) Non-modifiable • Female • Untreated early menopause (<45) • Late menarche (>15) • Short fertile period (<30 years) • Family history of osteoporotic fracture Modifiable • Smoking • Low calcium intake Box 1: Risk factors for fracture related to low BMD Box 2: Risk factors for fracture at least partly independent of low BMD Non-modifiable • Older age • Prior osteoporotic fracture • Family history of hip fracture • Poor visual acuity* • Neuromuscular disorders* Modifiable • Low body weight • Use of corticosteroids • Cigarette smoking • Alcohol excess * Modifiable in some cases Guidelines for osteoporosis in inflammatory bowel disease and coeliac disease 3 June 2007 BSG Guidelines in Gastroenterology T ab le 2 : O cc u rr en ce o f o st eo p o ro ti c fr ac tu re s in I B D A u th o rs S tu d y p o p u la ti o n F ra ct u re F ra ct u re r is k i n C ro h n ’s d is ea se [ 95 % C I] F ra ct u re r is k i n u lc er at iv e co li ti s [9 5% C I] Ve st er ga ar d et al [ 27 ] Po pu la ti on -b as ed s u rv ey o f D an is h C ro h n ’s (n = 38 3) C ol it is ( n = 43 4) A ss oc ia ti on m em be rs A ll S pi n e Fo re ar m Fe m u r R R 1 .7 [ 1. 2 – 2. 3] W om en R R 2 .5 [ 1. 7 – 3. 6] Po st m en op au sa l R R 1 .8 [ 1. 0 – 3. 3] Fa m ily h is to ry R R 2 .4 [ 1. 4 – 4. 1] C u rr en t sm ok in g R R R R 1 .3 [ 0. 6 – 2. 8] R R 6 .7 [ 2. 1 – 21 .7 ] R R 2 .0 [ 0. 8 – 5. 1] R R 1 .5 [ 0. 2 – 11 .7 ] R R 1 .1 [ 0. 8 – 1. 6] W om en R R 1 .1 [ 0. 7 – 1. 8] Po st m en op au sa l R R 0 .6 [ 0. 3 – 1. 6] Fa m ily h is to ry R R 1 .9 [ 1. 0 – 3. 5] C u rr en t sm ok in g R R 3 .8 [ 1. 9 – 7. 8] R R 2 .4 [ 0. 5 – 11 .9 ] R R 1 .2 [ 0. 1 – 13 .8 ] R R 0 .6 [ 0. 1 – 4. 9] Ve st er ga ar d et al [ 28 ] D an is h i n -p at ie n t re gi st ry o f C ro h n ’s d is ea se (n = 70 72 ) an d u lc er at iv e co lit is ( n = 83 23 ) A ll S pi n e C ol le s Fe m u r IR R 1 .1 9 [1 .0 6 – 1. 33 ] IR R 1 .8 7 [1 .2 4 – 2. 82 ] IR R 1 .0 4 [0 .7 6 – 1. 43 ] IR R 1 .1 0 [0 .8 7 – 1. 38 ] IR R 1 .0 8 [0 .9 7 – 1. 20 ] IR R 1 .0 4 [0 .6 7 – 1. 62 ] IR R 1 .0 2 [0 .7 6 – 1. 37 ] IR R 1 .0 8 [0 .8 8 – 1. 32 ] B er n st ei n e t al [ 29 ] C an ad ia n p op u la ti on -b as ed c oh or t st u dy ( n = 60 27 ) A ll S pi n e Fo re ar m H ip IR R 1 .3 6 [1 .1 7 – 1. 59 ] IR R 1 .5 4 [1 .0 4 – 2. 30 ] IR R 1 .3 0 [1 .0 1 – 1. 66 ] IR R 1 .4 7 [1 .0 3 – 2. 10 ] IR R 1 .4 5 [1 .2 6 – 1. 67 ] IR R 1 .9 0 [1 .3 6 – 2. 65 ] IR R 1 .3 6 [1 .0 6 – 1. 73 ] IR R 1 .6 9 [1 .2 6 – 2. 28 ] Lo ft u s et a l [3 0] A m er ic an p op u la ti on -b as ed c oh or t st u dy ( n = 23 8) A ll S pi n e Fo re ar m Fe m u r R R 0 .9 [ 0. 6 – 1. 4] R R 2 .2 [ 0. 9 – 5. 5] R R 1 .8 [ 0. 5 – 6. 1] R R 0 .2 [ 0. 03 – 2 .2 ] Va n S ta a et a l [3 1] U K p op u la ti on -b as ed c oh or t st u dy u si n g G P R D (n = 72 5 C ro h n ’s d is ea se ; n = 13 05 u lc er at iv e co lit is ) A ll S pi n e R ad iu s H ip O R 1 .4 [ 1. 2 – 1. 6] O R 1 .9 [ 1. 1 – 3. 2] O R 1 .4 5 [1 .0 – 2 .0 ] O R 1 .8 6 [1 .0 8 – 1. 21 ] O R 1 .2 [ 1. 05 – 1 .3 ] O R 1 .4 [ 0. 9 – 2. 2] O R 1 .2 [ 0. 9 – 1. 5] O R 1 .4 0 [0 .9 2 – 2. 13 ] C ar d et a l [3 2] U K p op u la ti on -b as ed c oh or t st u dy u si n g G P R D (n = 59 60 C ro h n ’s d is ea se ; n = 83 01 u lc er at iv e co lit is ; in de te rm in at e n = 22 89 ) H ip H R 2 .0 8 [1 .3 6 – 3. 18 ] A dj u st ed H R 1 .6 8 [1 .0 1 – 2. 78 ] H R 1 .4 9 [1 .0 4 – 2. 15 ] A dj u st ed H R 1 .4 1 [0 .9 4 – 2. 11 ] K la u s et a l [3 3] H os pi ta l- ba se d ca se s er ie s in G er m an y of p at ie n ts w it h T s co re < -1 .0 ( n = 15 6) S pi n e P re va le n ce 2 1. 8% ( n = 34 ) am on g th os e w it h T s co re < -1 .0 S to ck br u gg er et a l [3 4] M u lt ic en tr e E u ro pe an /I sr ae li h os pi ta l ba se d st u dy (n = 27 1) S pi n e P re va le n ce o ve ra ll 14 % 25 /1 79 s te ro id -f re e (1 4% ) 13 /8 9 st er oi d de pe n de n t (1 4. 6% ) RR = r el at iv e ris k; IR R = in ci de nc e ra te r at io ; O R = od ds r at io ; H R = ha za rd r at io 4 NR Lewis, BB Scott BSG Guidelines in Gastroenterology June 2007 Table 3: Cross-sectional survey of the prevalence of reduced BMD in Crohn’s disease patients using DEXA 1Patients with a preserved colon; 2Patients with a resected colon; 3did not receive steroids; 4received steroids; 5p < 0.05 on comparison of z-score with controls; 6control Authors Country Number of patients DEXA site Mean age (years) +/- SD Mean disease duration (years) +/- SD Mean Z-score Mean T-score % osteo- porosis % osteo- penia Pigot et al [35] France 27 Spine Femoral neck 34 +/-13 5.3 +/-6.3 -1.11 -0. 83 Ghosh et al [36] Scotland 15 Spine Forearm 24 0.36 -1.1 -1.1 Bernstein et al [37] USA 26 Spine Total hip -1.1 -1.5 Roux et al [38] France 14 Spine Femoral neck -1.12 -1.01 Silvennoinen et al [39] Finland 78 73 6 Spine Femoral neck 38.6 +/-8.7 40.8 +/-9.3 11.5 +/-6.0 -0.18 0.406 -0.43 0.12 6 Staun et al [40] Denmark 40 1 68 2 Spine Femoral neck 40.1 +/-13.2 36.5 +/-12.3 13 +/-8.4 11.8+/-7.2 -0.51 -0.80 -1.24 -1.23 Jahnsen et al [41] Norway 60 60 6 Spine Femoral neck 36 36 6 -0.07 3,5 -0.52 4,5 -0.17 3,5 -0.97 4,5 Robinson et al [42] England 117 Spine Femoral neck Trochanter 40.6 +/-13 9.6 -0.09 -0.20 -0.30 12 29 Schulte et al [43] Germany 104 Spine Femoral neck 38 +/-15 11.5 +/-8 15 12 36 Schulte et al [44] Germany 61 Spine Femoral neck -0.70 -0.55 Pollak et al [45] Israel 33 Spine Femoral neck 37.4 +/- 4.9 8.4 +/-8.1 -1.4 -1.8 -2.26 -2.49 57.6 36.4 Dinca et al [46] Italy 54 Spine 39 +/-2 6.6 +/-0.7 -0.90 -1.16 5.5 42.5 Lee et al [47] Korea 14 Spine Femoral neck 2.17 +/-0.25 -0.61 0.03 -0.96 -0.07 0 50 Ardizzone et al [48] Italy 51 Spine Femur 38.7 +/-13.2 39.4 +/-11.6 7.0 +/-5.6 -1.24 -1.24 -1.49 -1.80 37 55 Schoon et al [49] Netherlands 24 Total body Spine Femoral neck 29.7 +/-10.4 0.41 0.5 0.13 0.0 Schoon et al [50] Netherlands 119 Spine Femoral neck Total body 42 +/-14 10.5 +/-8.8 0.00 -0.52 -0.27 -0.42 -0.96 -0.50 7 11 6 22 41 27 Haugeberg et al [51] Norway 55 Spine Femoral neck Total hip 38.5 +/-12.7 9.1 +/-7.4 -0.51 -0.58 -0.23 5.5 9.1 5.5 Schoon et al [452] Netherlands 26 Spine Femoral neck Total body 38 +/12 16 +/-8 -0.43 -0.90 -0.38 -0.71 -1.03 -0.67 15 4 8 23 31 27 De Jong et al [53] Netherlands 91 Spine Femoral neck 41.3 +/-13.3 11.6 +/-8.5 -1.1 -1.1 20 25 40 47 Jahnsen et al [54] Norway 60 Spine Femoral neck Total body 36 10 0.05 -0