OSTEOPOROSIS. Case study 69 report. October 2011

Transcription

1 OSTEOPOROSIS Case study 69 report October 2011 Independent, not-for-profit and evidence based, NPS enables better decisions about medicines and medical tests. We are funded by the Australian Government Department of Health and Ageing. Level 7/418A Elizabeth St Surry Hills NSW 2010 PO box 1147 Strawberry Hills NSW 2012 P F National Prescribing Service Limited. ABN NPSCS1221

2 2011 National Prescribing Service Limited This work is copyright. You may download, display print and reproduce this work in unaltered form (only retaining this notice) for non-commercial use either personally or within your organisation. Apart from any such use or otherwise as permitted under the Copyright Act 1968, all rights are reserved. This work may contain other works (subworks) reproduced with permission from third party copyright owners. Please ensure that you have permission from the copyright owner or pursuant to the Copyright Act before using such subworks. Queries concerning reproduction and rights should be sent to Suggested citation National Prescribing Service Limited. Case study report, case study 69: Osteoporosis. Sydney: NPS, October, Acknowledgments NPS, Better choices, Better Health would like to acknowledge expert commentaries provided by the following reviewers: Dr. Simon Vanlint, Assistant Dean, Lecturer, Discipline of General Practice, University of Adelaide, South Australia Professor John Eisman, Senior Research Fellow; Director, Bone Research Program, Garvan Institute of Medical Research; Professor of Medicine, The University of New South Wales, Endocrinologist, St Vincent s Hospital, Sydney. 2

3 Contents Case study 69: Osteoporosis...3 Summary of results... 6 Results in detail... 7 Assessing absolute fracture risk... 7 Advice on lifestyle interventions to reduce risk of fracture... 7 Anti-osteoporotic drug therapy... 9 Risk factors and strategies to reduce fracture risk Commentaries Dr. Simon Vanlint Professor John Eisman References

4 CASE STUDY 69 OSTEOPOROSIS SCENARIO Bill is a 72-year-old retired train driver who was admitted to hospital six months ago after fracturing his hip, when his foot got caught on a floor mat at home. Bill has been reluctant to walk every evening since this fall. He has been a smoker for 30 years and smokes 15 cigarettes every day. Bill lives alone in the self-catered accommodation part of a retirement village and has lost about 5 kg of weight in the past few months. His diet has deteriorated since his wife passed away two years ago. Bill s daughter accompanies him to visit his GP, as she is concerned about his recent weight loss. His current medicine history includes ramipril 5 mg once daily in the morning for wellcontrolled hypertension, and occasionally temazepam 10 mg at bedtime to help him sleep. On examination Bill s blood pressure is 115/78 mmhg and he has no significant family medical history. His vitamin D level is moderately deficient (22 nmol/l) and a bone mineral density test T-score in the hip is 1.8 and in the spine is 2.7, confirming a diagnosis of osteoporosis. 1. How would you assess Bill s future absolute risk of fracture? FRAX (WHO fracture risk assessment tool) Garvan Institute fracture risk calculator Clinical assessment of risk factors (Please specify) Other, please specify 2. What information would you provide to Bill regarding his: Physical activity: Calcium intake: Vitamin D intake 4 CASE SCENARIO AND QUESTIONS

5 3. Is Bill a candidate for an osteoporotic drug (examples below)? yes no If yes, please indicate which agent you would consider (you may select more than one option) alendronate risedronate zoledronic acid teriparatide other (specify) 4. List three risk factors (different to those in Q2) that increase Bill s fracture risk and your recommendation to reduce this risk Risk factor: Recommendation: Risk factor: Recommendation: Risk factor: Recommendation: CASE SCENARIO AND QUESTIONS 5

6 SUMMARY OF RESULTS At the time of publication 1261 responses had been received from all participants, and 200 of those received from doctors have been compiled for feedback in this report. CASE SYNOPSIS Bill is a 72-year-old retired train driver who was admitted to hospital six months ago after fracturing his hip, when his foot got caught on a floor mat at home. Bill has been reluctant to walk every evening since this fall. He has been a smoker for 30 years and smokes 15 cigarettes every day. Bill s daughter accompanies him to visit his GP, as she is concerned about his recent weight loss. His current medicine history includes ramipril 5 mg once daily in the morning for wellcontrolled hypertension, and occasionally temazepam 10 mg at bedtime to help him sleep. A bone mineral density test (T-score of 1.8 in the hip and 2.7 in the spine) confirmed the diagnosis of osteoporosis. (See page 3 for more details.) Assessing absolute fracture risk Almost half (46%) of respondents reported conducting a clinical assessment of risk factors to assess Bill s fracture risk. Additionally 27% and 24% of respondents, respectively, reported using FRAX (WHO fracture risk assessment tool) and Garvan Institute fracture risk calculators to assess Bill s fracture risk. Advice on lifestyle interventions to reduce risk of fracture Almost half (44%) of respondents advised Bill to resume walking (low-impact weight-bearing exercises). Thirty-three per cent of participants suggested combining high-intensity strength (resistance) training with walking. Thirty-eight per cent of respondents recommended Bill to increase his dietary intake of calcium (three serves of low-fat products), while 22% of participants recommended a calcium supplement ( mg) daily. Half of the respondents (50%) recommended a vitamin D supplement for Bill, while 32% of participants advised him to increase exposure to sunlight in addition to taking a vitamin D supplement. Anti-osteoporotic drug therapy Most respondents (95%) considered anti-osteoporotic drug therapy appropriate for Bill. Of these, 49% and 32% of participants, respectively, chose alendronate and risedronate. Risk factors and strategies to reduce fracture risk Most respondents (98%) listed three risk factors that may increase Bill s fracture risk. Thirty per cent of respondents indicated smoking as a significant risk factor for fractures and recommended Bill to quit smoking with the aid of a smoking-cessation program. Eighteen per cent of respondents identified use of benzodiazepines as a potential risk factor and suggested that they would review the need of benzodiazepines and discuss sleep hygiene with Bill. 6 SUMMARY OF RESULTS

7 RESULTS IN DETAIL Assessing absolute fracture risk Respondents were asked how they would assess Bill s absolute fracture risk. Nearly half (46%) of respondents indicated conducting a clinical assessment to identify risk factors to assess Bill s fracture risk. Table 1 shows the proportion of participants and their choice of assessments conducted to determine Bill s fracture risk. TABLE 1: ASSESSMENTS SUGGESTED BY RESPONDENTS TO DETERMINE FRACTURE RISK Assessments % of respondents (n = 200)* Clinical assessment of risk factors 46 FRAX (WHO fracture risk assessment tool) 27 Garvan Institute fracture risk calculator 24 Other (specify) 3 * Respondents may have more than one response Clinical risk factors included modifiable (e.g. smoking, sedentary lifestyle and excessive alcohol intake) and non-modifiable (e.g. previous fracture and advanced age) risk factors Others included annual percentage of hip fractures and general state of health Practice points Conduct a comprehensive fracture risk assessment, as presence of one major risk factor (e.g. low bone mineral density [BMD]) does not reliably predict overall fracture risk. 1 Consider using a fracture risk calculator as part of the overall assessment of risk. FRAX (WHO fracture risk assessment tool) and Garvan Institute fracture risk calculator are available online. For more information on FRAX assessment tool please refer to and for Garvan Institute fracture risk calculator. Review modifiable (smoking, alcohol intake and physical activity) and non-modifiable (previous fracture) risk factors for fractures. 2 Advice on lifestyle interventions to reduce risk of fracture Physical activity Respondents were asked to indicate the type of information they would provide to Bill regarding level of physical activity, calcium and vitamin D intake to prevent fractures. Table 2 shows that nearly half (44%) of respondents advised Bill to resume walking (low-impact, weight-bearing), while 33% suggested combining high-intensity strength (resistance) training with walking. TABLE 2: TYPES OF PHYSICAL ACTIVITY SUGGESTED BY RESPONDENTS Type of activity % of respondents (n = 200) Low-impact weight-bearing exercise (walking) 44 Walking combined with high-intensity strength (resistance) training 33 Increased physical activity 19 High-intensity strength (resistance training) 2 Others* 2 * Others included need to assess risk of falls and passive exercise (not weight bearing). RESULTS IN DETAIL 7

8 Practice points Encourage people with osteoporosis to exercise regularly to build strong bones. 2 Recommend low-impact weight-bearing exercises combined with high-intensity strength (resistance) training, as it conserves BMD. 3,4 Encourage people to consult a physiotherapist or exercise physiologist to design a program specific to their needs, abilities and interests. 5 Advise people that high-impact loading (running), dynamic abdominal exercises (sit-ups), twisting movements (golf swing), trunk flexion (some exercise machines) are unsuitable for people diagnosed with osteoporosis. 2 Calcium and vitamin D intake Thirty-eight per cent of respondents recommended Bill to increase his dietary intake of calcium (three serves of low-fat products), while 22% of participants recommended a calcium supplement ( mg) daily for Bill, as shown in Table 3. TABLE 3: CALCIUM INTAKE SUGGESTED BY RESPONDENTS Calcium intake % of respondents (n = 198) Three serves of dairy per day 38 Calcium supplementation ( mg daily) 22 Three serves of dairy or calcium supplementation 18 Supplementation when dietary intake of calcium is not possible 12 Both three serves of dairy and supplementation 10 Table 4 shows that 50% of respondents recommended Bill to start taking a vitamin D supplement daily, while 32% advised him to increase exposure to sunlight in addition to a vitamin D supplement. TABLE 4: VITAMIN D INTAKE SUGGESTED BY RESPONDENTS Vitamin D intake % of respondents (n = 196) Vitamin D supplementation 50 Increase exposure to sunlight and supplementation 32 Supplementation OR exposure to sunlight 10 Increased exposure to sunlight 8 Practice points Recommend adequate dietary intake of calcium for people with osteoporosis. Three serves of dairy food daily provides enough calcium for most adults. 1 Consider calcium supplements for people who are unable to get adequate calcium from their diet. Recommend adequate sun exposure or vitamin D intake in people at risk of deficiency, especially for people diagnosed with osteoporosis. 6 For more information on recommended daily intake of calcium, please refer to the Osteoporosis Australia website ( 6 For more information about vitamin D, please refer to NPS News 72: Testing and treating vitamin D deficiency ( 7 8 RESULTS IN DETAIL

9 Anti-osteoporotic drug therapy Most respondents considered anti-osteoporotic drug therapy for Bill. Table 5 shows that 49% and 32% of respondents selected alendronate and risedronate respectively. TABLE 5: ANTI-OSTEOPOROTIC DRUG THERAPY FOR BILL SUGGESTED BY RESPONDENTS Drug % of respondents (n = 199)* Alendronate 49 Risedronate 32 Zoledronic acid 16 Others 2 Teriparatide < 1 * Respondents may select more than one response (only one anti-osteoporotic drug can be prescribed at a time to meet the PBS criteria for subsidy) Others included strontium 4 g sachets Practice points Consider anti-osteoporotic drug therapy in people who have experienced an osteoporotic fracture. 8 Choose an anti-osteoporotic drug based on age, gender, medical history and personal preference. For more information on drug doses and routes of administration refer to NPS RADAR ( or the Australian Medicines Handbook. 9 Recommend patients to continue with anti-osteoporotic drug therapy, by highlighting the benefits of adherence rather than the negative consequences of stopping. 10 Provide information to people experiencing adverse effects of anti-osteoporotic drug therapy. Consider other drugs, routes of administration or dosing regimens for people complaining of dosing inconvenience or those unable to manage adverse effects. 9 Osteonecrosis of the jaw is a rare but serious side effect of bisphosphonate therapy. For more information see the NPS fact sheet on osteonecrosis. 11 RESULTS IN DETAIL 9

10 Risk factors and strategies to reduce fracture risk Respondents were asked to identify three risk factors that may increase Bill s risk of fracture and to list strategies to reduce the risk. Tables 6 and 7 summarises the additional risk factors and strategies to reduce fracture, respectively. Thirty per cent of respondents indicated that smoking was a significant risk factor and recommended Bill to quit smoking. Some respondents advised Bill to enrol in a smoking-cessation program, while others recommended using medicines such as bupropion or varenicline. Eighteen per cent of participants identified occasional use of benzodiazepines as a potential risk factor for a fracture and recommended reviewing the ongoing need of benzodiazepines. Few participants indicated that they would discuss sleep hygiene with Bill. TABLE 6: ADDITIONAL RISK FACTORS SUGGESTED BY RESPONDENTS Additional risk factor % of respondents (n = 198)* Smoking 30 Use of benzodiazepines 18 Weight loss associated with poor diet 17 Falls hazards in the home 7 Use of antihypertensive causing postural hypotension 7 Increased risk of falls 6 Sedentary lifestyle 5 Previous fracture, low BMD and osteoporosis 5 Others 4 * Respondents may have more than one response Others included advanced age, alcohol intake, previous medical conditions, and living arrangements TABLE 7: STRATEGIES SUGGESTED BY RESPONDENTS TO REDUCE FRACTURE RISK Strategy to reduce fracture risk % of respondents (n = 197) Quit smoking* 30 Review (reduce/stop) the use of benzodiazepines and discuss sleep hygiene 18 Encourage to improve diet 17 Home assessment to identify risk factors for falls 12 Review the dose of antihypertensive and monitor blood pressure 8 Encourage to improve lifestyle 7 Start an anti-osteoporotic drug 5 Others 3 * Respondents may have more than one response Others including lower caffeine intake and no recommendations for a non-modifiable risk factor such as age Practice points Conduct a multifactorial risk assessment followed by intervention directed towards identified risk factors. Examples of risk factors reviewed include a person s lifestyle (smoking and alcohol intake) and their medical condition. 12 Encourage individuals to enrol in a smoking-cessation program and exercise regularly to reduce risk of fractures. 10 RESULTS IN DETAIL

11 Assess people for risk of falls as it is one of the most important strategies for reducing fracture risk. 3 Review medicines that may increase risk of falls such as use of benzodiazepines and antihypertensives. 1 Encourage people to attend a falls clinic and enrol in a falls-prevention program. Such programs are tailored to the individual s needs. 12,13 For more information on measures that may be a part of the multifaceted falls-prevention program, refer to NPS PPR 54: Osteoporosis at RESULTS IN DETAIL 11

12 COMMENTARY 1 Key points Assessment of fracture risk should be multifactorial, taking into account factors such as: age gender history of falls previous fractures use of glucocorticoids smoking history alcohol use. Allied health referrals (physiotherapy, exercise physiology, occupational therapy) using chronic disease management plans and the Extended Primary Care program can help patients receive tailored expert advice. While the idea of sunlight exposure is appealing, in practice the skin s ability to synthesis vitamin D reduces with age, and adherence to sun exposure recommendations appears to be poor, 14 suggesting that vitamin D supplementation is often necessary in older people. Medication use contributes to falling, and thus to fractures. Bill s story raises issues that are important for many patients with osteoporosis. It is important to remember that both morbidity and mortality after a fractured neck of femur are significant, with estimates of mortality after such a fracture in elderly men of about 30%. Those who do survive generally do not recover their premorbid level of function or quality of life and often require significant additional care. 15 Assessing Bill s risk of fracture Although 46% of respondents indicated they would assess fracture risk clinically, integrating all these factors is a complex task, and doctors could make more use of risk calculators like the Garvan Institute and FRAX tools, as did 51% of respondents. Dr. Simon Vanlint Assistant Dean Lecturer, Discipline of General Practice University of Adelaide, Adelaide, SA Only 33% of participants correctly identified that Bill should be advised to combine walking with high-intensity strength (resistance) training, suggesting that this approach could be used more widely. Many doctors will feel they lack the time and/or level of detailed expertise to provide patients with a detailed exercise prescription. Similarly, an occupational therapy assessment of his home may help preserve mobility and assist in preventing further falls. Bill s poor diet and weight loss might also be a trigger for consultation with a dietitian. Adequate intake of protein, in addition to calcium, is important for muscle and bone health. Vitamin D levels are often reduced in older individuals, as was the case for Bill. Vitamin D is difficult to obtain from diet, leaving sunshine or supplementation as the realistic options. While the idea of sunlight exposure is appealing, in practice the skin s ability to synthesis vitamin D reduces with age, and adherence to sun exposure recommendations appears to be poor, 14 suggesting that vitamin D supplementation is often necessary in older people. Daily doses of IU are recommended, although higher doses may be required to correct existing deficiency. Compounding pharmacists will make up larger doses, typically 100,000 IU per dose. While it appears that giving 100,000 IU every 3 months is safe, 16 an oral dose of 500,000 IU annually was shown in a recent Australian study to temporarily increase the risk of falling and fractures in the elderly, 17 so the optimal dose and interval remain unclear. Bill s vitamin D level could be checked after 2 3 months to ensure it has reached target levels, which for bone health and falls prevention probably means values > 60 nmol/l. 18,19 Eighteen per cent of respondents correctly identified Bill s use of a benzodiazepine (temazepam) as a risk factor for further falls and fractures, but few indicated that they would 12 COMMENTARY 1

13 discuss sleep hygiene with him. This may be due to a perceived lack of alternatives to benzodiazepine use. NPS has developed a site with useful resources for consumers and a downloadable sedative reduction plan for health professionals, located at Bill s blood pressure today was normal, but it is possible he may sometimes experience postural hypotension. Reviewing the dose of his antihypertensive (ramipril) and possibly trialling a cessation may be helpful. The ANBP2 study found that 18% of patients remained normotensive after stopping their antihypertensives. 20 Individuals using five or more regular medications may be referred to a pharmacist for a thorough medication review. Managing patients like Bill is important, but preventing osteoporotic fractures like his is even more important. Assessing elderly patients for falls risk (mobility, vision, balance, medications) is likely to be helpful, and medicare funding is available for DEXA bone mineral density screening in people aged 70 and over, as well as at-risk younger individuals. Vitamin D insufficiency and deficiency are common in the elderly, and such individuals should be considered for screening and/or supplementation, especially those in residential aged-care facilities. In 2007 the direct cost of osteoporosis was estimated be $1.9 billion per annum, with indirect costs (especially of increased need for care/supervision) likely to substantially inflate this figure. 21 Health professionals could improve both screening and primary prevention and treatment of those who sustain fragility fractures, with significant benefits for individuals, families and the general community. COMMENTARY 1 13

14 COMMENTARY 2 Key points Osteoporosis is common in men, with about one-third of fragility fractures occurring in men. After a single fracture the subsequent risk of another fracture in men increases about fourfold so that it exceeds the risk in women of the same age and is the same as in a woman who has also suffered a fracture. Fragility fractures also signal a 2-3-fold risk of premature mortality, that is, compared with other men of the same age. This increase is more marked in men than in women, and lifeyears-lost are greatest in relatively young old. Vitamin D insufficiency is common and requires adequate replacement as a first priority. This would commonly require IU daily for at least several weeks before stabilising on IU daily. Normalisation of the 25-hydroxyvitamin D (25-OHD) level should be monitored. In view of the severity of Bill s deficiency, major causes should be excluded, for example, malabsorption such as coeliac disease. Normalisation of vitamin D level, as well as effects on bone and being required for optimal response to specific therapy, can improve muscle strength that will be critical during rehabilitation and also reduce falls risk. Attention to lifestyle should include diet, alcohol and tobacco use and adequate physical activity. Causes of secondary osteoporosis, including low testosterone, malabsorption as in coeliac disease, glucocorticoid use and inflammatory states each deserve careful consideration and exclusion or specific treatment if possible. The occurrence of a fragility fracture should lead to initiation of specific anti-osteoporosis therapy, unless there is a major contraindication. If Bill had had his BMD measured before his fracture and if his T-score was < 3 at any site, he would have been eligible for specific therapy and could have avoided this first fracture. Professor John Eisman Director, Bone Research Program Garvan Institute of Medical Research Professor Of Medicine, The University of New South Wales The Garvan fracture risk calculator or WHO FRAX tools can be used to estimate the individual patient s absolute risk of future fracture. This may help the discussion with the patient about options for treatment. General comments This case represents very typical osteoporosis in that Bill has experienced a fracture with minimal trauma. It is perhaps not recognised that his risk of dying is three times that of other men of his age, independent of any other health practices or comorbidities. One can assess his future absolute risk of fracture using the Garvan Fracture Risk Calculator. However, his case meets the formal definition of a fragility fracture and should be given specific treatment. Bill is clearly vitamin D deficient, with a 25-OHD level of 22nmol/L, and vitamin D replacement should be the initial and urgent step. This would have benefit for his bones and would improve proximal muscle strength that will be critical during his rehabilitation. The possibility of Bill having a T-score < 3 at any site raises the important clinical management point that any man (or woman) aged 70 years or over is eligible for a Medicare-reimbursed bone mineral density (BMD) test. If their T-score is < 3 they are eligible for PBS-subsidised pharmacological treatment without having the need to have already experienced a fracture. Investigations Measurement of BMD helps distinguish between fractures associated with major versus minimal trauma. Lateral X-ray of the thoracic and lumbar spine should be performed, particularly if the patient has lost height since peak height in early adulthood. One is seeking evidence of vertebral deformities, including clinically silent spine fractures, that also signal major increase in fracture risk. 14 COMMENTARY 2

15 Biochemical parameters are useful to identify alterations in calcium and parathyroid function (calcium, ipth, creatinine, 25-OHD),and to exclude: coeliac disease (AntiTTG, IgA) thyroid dysfunction (TSH, ft4) hypogonadism (testosterone, LH) immune disorders, including myeloma (iepg). Markers of bone turnover are useful but more for assessment of response to treatment. The lower the BMD compared with agematched controls (Z-score), the stronger the imperative to seek potentially treatable causes of secondary osteoporosis. Most reliable diagnostic tools Bone density and spine X-rays The lower the bone density T-score (comparison to young normal mean) the more severe the osteoporosis. While a T-score of < 2.5 meets the formal definition of osteoporosis, many fragility fractures that warrant specific anti-osteoporosis therapy occur with BMD above this level. In Australia a BMD T-score < 3.0 meets PBS criteria for treatment in men (and women) aged 70 years or older even if they have not had any fractures. The presence of vertebral deformities on spine X-rays meets PBS criteria for treatment in men (and women) irrespective of measured bone density. Additional questions A history of osteoporotic fracture in the family can help identify those at increased risk before the first fracture. A history of prior fractures should be specifically sought, as it may not be volunteered, and is a signal of heightened further fracture risk. A history of falls should also be sought (again it will seldom be offered), as it is a major contributor to fracture risk, particularly in men. Recommended drug therapy Once the decision is made for treatment in men, the choice rests between various bisphosphonates. Other treatments available for women (strontium ranelate and denosumab) are expected to be useful in men but have not yet been validated in men. The choices between oral and intravenous bisphosphonates are influenced by clinical factors such as preference for weekly or monthly by mouth, or annually by intravenous infusion. Oral bisphosphonates (alendronate [Fosamax] and risedronate [Actonel]) must be taken in the fasted state with plain water, and the patient must remain upright and wait 30 minutes to an hour before eating. Even when taken in this way, bisphosphonates are poorly absorbed. However, if taken incorrectly, absorption is so poor as to be negligible. A novel enteric-coated formulation of one of the bisphosphonates (risedronate, Actonel EC) that includes EDTA can be taken with food, for example, breakfast. Absorption and clinical response are comparable to those of the normal oral formulation taken fasting. The intravenous bisphosphonate, zoledronic acid (Aclasta), is given as a once-yearly infusion. This avoids any problems with upper gastrointestinal issues and poor absorption related to method of administration and allows the doctor to be sure of the patient s compliance with therapy. Both alendronate and risedronate are available as formulations and packaging that provide a regular supplement of vitamin D (equivalent to 800 IU daily) and calcium supplements (if required). COMMENTARY 2 15

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