OSTEOPOROSIS GUIDELINES

Dr J P Halsey, Consultant Rheumatologist, Royal Lancaster Infirmary Dr C Rao, Consultant Rheumatologist, Blackpool, Fylde & Wyre Hospitals NHS Foundation Trust & Melanie Greenall, Governance Pharmacist, NHS North Lancashire

February 2011 Due for review February 2013

(or in light of changes in best practice recommendations)

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CONTENTS

1. The need for Osteoporosis Management Guidelines (p3) 2. Management Algorithm (p4) 3. Supplementary Notes to Algorithm (p5-p8) 4. Corticosteroid Induced Osteoporosis (p9-p11) 5. Aromatase Inhibitor Guidelines (p11) 6. Specialist Referral Guidelines (p11) 7. References (p12) 8. Information Resources for Patients and Carers (p13)

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1. The Need for Osteoporosis Management Guidelines Osteoporosis is defined as a progressive systemic skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis is widely recognised as a major clinical problem and guidelines on primary and secondary prevention have been produced by the National Institute for Clinical Excellence (NICE TA160 & TA 161), the Map of Medicine and the National Osteoporosis Guideline Group (NOGG). The WHO has produced a fracture risk calculator (FRAX) and NOGG have provided guidance on how this should be used in clinical practice. In the United Kingdom osteoporosis results in over 200,000 fractures each year, causing severe pain and disability to individual sufferers at an annual cost of 2.3 billion. More than one third of adult women will sustain one or more osteoporotic fractures in their lifetime. Lifetime risk in men is less and approximately half that of women. Common fractures include vertebral compression fractures and fractures of the wrist and hip. Hip fractures have a high mortality and alone account for more than 20% of Orthopaedic bed occupancy in the UK and the majority of the direct health service cost of osteoporosis. The ageing population will give rise to a doubling of the number of osteoporotic fractures over the next 50 years if changes are not made in present practice. For diagnostic purposes, two thresholds of bone mineral density (BMD) have been defined by the World Health Organisation: Osteoporosis - BMD 2.5 standard deviations (SDs) or more below the young adult mean value, i.e. Tscore less than -2.5 Low bone mass, or osteopenia - T-score that lies between -1 and -2.5. From a practical perspective osteopenia is not referred to in these guidelines as it does not influence management and patients falsely consider that this term represents a disease that needs treating. Although (BMD) is the most important determinant of fracture risk, many other factors including liability to falls and types of fall also contribute to the risk. The aetiology of osteoporotic fractures is multi-factorial and strategies to tackle osteoporosis should take these factors into account. These guidelines represent an amalgamation of NICE and NOGG guidelines. Whilst adhering to the principles laid down by NICE they are more workable in clinical practice and include guidelines for women, men, corticosteroid induced osteoporosis and guidelines for aromatase inhibitors. The proposed management algorithm is for women and men for both primary and secondary prevention. Separate algorithms are available for corticosteroid induced osteoporosis and the management of women receiving aromatase inhibitors.

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2. Osteoporosis Management Algorithm for Postmenopausal Women and Men > 50yrs old

Fragility fracture

No Fragility fracture

Age 75

Age <75

> 1 clinical risk factor2

Measure BMD by DEXA3 Assess for underlying causes4 Lifestyle advice5 Falls advice Treat8-9 Estimate fracture risk using FRAX7
6

Osteoporosis (T-score <-2.5)

No Osteoporosis

High fracture probability

Low fracture probability

3 month assessment ? therapy compliance13 Second line treatments10-17

Reassure Lifestyle advice5

These guidelines should not replace clinical judgement

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3. Supplementary Notes to Algorithm 1. Definition A low trauma fracture or fragility fracture is defined as a fracture (particularly those occurring in unusual locations e.g. spine, hip, pelvis) due to a low energy event (e.g. a fall from a standing height or less: rib fracture due to sneezing or coughing). 2. Clinical Risk Factors (CRF) for Osteoporosis (NICE emphasises items in Bold) Low body mass index (22kg/m) Previous fragility fracture, particularly of the hip, wrist and spine Parental history of hip fracture X-ray evidence of osteopenia and/or changes in vertebrae consistent with fracture Current corticosteroid treatment (any dose, by mouth for 3 months or more) Alcohol intake of 4 or more units daily Secondary causes of osteoporosis including: Rheumatoid arthritis Untreated hypogonadism in men and women Prolonged immobility Post transplant (bone or organ) Type I diabetes Hyperthyroidism Primary hyperparathyroidism Coeliac disease and other causes of malabsorption Anorexia nervosa Chronic liver disease Chronic renal failure Chronic obstructive pulmonary disease Some medications that can induce vitamin D deficiency e.g. anticonvulsants Falls not a risk factor for assessment purposes, but needs to be considered 3. Assessment of Bone Density should be performed by DEXA, preferably on two sites at the anteroposterior spine and hip. Assessment by ultrasound, peripheral DEXA or Quantitative Computerised Tomography (QCT) is not appropriate and does not form part of this guidance. Follow up DEXA scans are not recommended to assess the response to treatment. Follow up scans are indicated for patients receiving corticosteroids and aromatase inhibitors see separate guidance attached as appendices For patients > 75yrs who have sustained a low trauma fracture referral for DEXA should be considered for all cases (Ralston et al, 2009) who are able to attend for scanning and get on the scanning table unaided. This would result in approximately 50% women not being started on treatment unnecessarily (Ralston et al, 2009). 4. Before Initiating Treatment it is important to: Identify causes of secondary osteoporosis, e.g. hyperparathyroidism, alcohol abuse, thyroid disease Exclude other diseases which may mimic osteoporosis, including osteomalacia, by performing a range of tests depending on the severity of the disease, age at presentation and the presence/ absence of fractures. i. These tests are full blood count, ESR, renal function, calcium, phosphate, alkaline phosphatase. ii. Other investigations when clinically indicated may include Vitamin D assay, PTH, thyroid function tests, liver function tests, testosterone in men <60yrs, coeliac screen, and immunoglobulins & urine electrophoresis when ESR elevated.

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5. Lifestyle Advice Advice about lifestyle changes patients can make to help themselves should be offered to all individuals suffering from osteoporosis before treatment is commenced. This should include: Stop smoking Avoid excess alcohol and caffeine intake Regular weight bearing exercise Avoid immobility Maintain a healthy diet, aiming for a body mass index (BMI) 20-25kg/m Maintain an adequate intake of calcium and vitamin D 6. For Individuals Prone to Falling, consideration should be given to NICE CG21. Target those at greatest risk of falling, especially those with previous falls history by Avoiding polypharmacy - modifications of medicines regimen if possible to reduce drugs with sedative or adverse visual effects or those that increase urinary frequency Considering walking aids and well fitting shoes Correcting visual impairment Strength and balance exercises Considering the importance of a safe living environment Cardiology workup if cardiac cause for falls suspected 7. Assessment of Risk To estimate the 10yr absolute fracture risk for all osteoporotic fractures and hip fracture the FRAX tool can be accessed at www.shef.ac.uk/FRAX. It should be noted that caution needs to be exercised when using this tool for patients with vertebral osteoporosis/ fractures as the tool uses hip BMD results to calculate fracture risk rather than spine BMD which may result in under treatment of these patients. FRAX has only been validated for patients who are treatment nave and not for those who have been receiving treatment for osteoporosis. Using this tool could be useful in determining which patients identified for primary prevention should be referred for DEXA 8. Treatment Options Alendronic acid 70mg weekly is recommended as the first treatment option. It is important that patients are given advice regarding the correct way to take the medication to minimise the risk of adverse reactions and to maximise the therapeutic effect. Contraindications to alendronate are: Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achalasia inability to stand or sit upright for at least 30 minutes hypersensitivity to any component of the product hypocalcaemia. It is not recommended in patients with renal impairment (GFR <35 ml/min). 9. Calcium & Vitamin D It is assumed that patients who receive treatment have an adequate calcium intake and are vitamin D replete. Unless clinicians are confident that patients who receive treatment meet these criteria, calcium and/or vitamin D supplementation should be considered. It could be assumed that all housebound patients and those in residential or nursing homes are vitamin D deficient and these should all receive calcium and vitamin D supplements. A variety of different supplements are available. A dose of at least 1g elemental calcium and 20mcg (800IU) vitamin D supplements should be given. It should be noted that calcium and vitamin D supplements are not in themselves a treatment option.

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10. Second Line Treatments Where alendronic acid is contraindicated or not tolerated, alternative oral treatments are Risedronate 35mg weekly or Strontium Ranelate 2G daily. Patients can be offered these alternative second line therapies, provided they meet the BMD/risk factor criteria outlined by NICE in TA 160 & TA 161. Intolerance is defined as persistent upper gastrointestinal disturbance that is sufficiently severe to warrant discontinuation of treatment, and that occurs even though the instructions for administration have been followed correctly Patients receiving these agents should receive appropriate counselling regarding the medication e.g. strontium should not be given to people with risk factors for venous thromboembolism (VTE) and very rarely hypersensitivity reactions may occur 11. Treatments to be Avoided There is insufficient evidence as to the efficacy of etidronate, ibandronate or raloxifene in the prevention of non vertebral fractures and these drugs should be avoided. 12. Other Treatments Other agents such as calcitriol and calcitonin have a very limited use in the management of osteoporosis and should be avoided outside specialist centres. 13. Monitoring of Treatment There is no evidence that routine monitoring of bone density improves the outcome of osteoporosis therapy and this should not be routinely offered. The role of bone turnover markers in the monitoring of osteoporosis therapy is unclear and should not routinely be used. In view of major compliance issues with bisphosphonate therapy and Calcium and vitamin D supplements it is recommended that a primary care led assessment is performed to maximise compliance at 3 months and 12 months and a review appointment made when indicated. 14. Treatment Failure It is important to realise that even the best treatments will only decrease the fracture rate (generally between 30% and 60% for oral bisphosphonates). NICE define an unsatisfactory response to treatment as occurring when a woman has another fragility fracture despite adhering fully to treatment for 1 year and there is evidence of a decline in BMD below her pre-treatment baseline. Patients who sustain a further low trauma fracture after one year of therapy should be offered a repeat DEXA scan. If the BMD has fallen significantly (exact cut off depends on the machine used and will be noted on the report), treatment can deemed to have failed and intravenous therapy or anabolic therapy with PTH offered. 15. Intravenous Therapy Patients should be referred to secondary care for administration of intravenous therapy with zoledronic acid which may be offered to patients annually with treatment failure, poor compliance or intolerance of oral therapy. Before administration of zoledronic acid patients must be vitamin D replete Contraindications to zoledronate are: Hypocalcaemia Pregnancy and lactation Severe renal impairment (creatinine clearance < 35mL/min) The dose is 5mg, given as an IV infusion over 15 minutes once each year There is insufficient evidence of non vertebral fracture reduction with either intravenous ibandronate or pamidronate and these should not be given

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16. Subcutaneous Therapy Denosumab is an alternative treatment option for the prevention of both primary and secondary osteoporotic fragility fractures in certain postmenopausal women who are unable to comply with the special instructions for administering oral bisphosphonates, or have an intolerance of, or a contraindication to, those treatments. Additionally for primary prevention, patients should have the combination of T-score, age and number of independent clinical risk factors for fracture outlined in NICE Technology Appraisal TA 204. Denosumab may be particularly useful in patients with severe renal disease where it is considered the safest option. Initial prescribing will be started in secondary care via a hospital outpatient appointment, with subsequent doses being delivered almost exclusively in primary care. The dose is 60mg given by subcutaneous injection every 6 months, by someone adequately trained in subcutaneous injection technique 17. Parathyroid Hormone Teriparatide is recommended as an alternative treatment option for the secondary prevention of osteoporotic fragility fractures in postmenopausal women according to the criteria laid down in TA161 i.e.: who are unable to take alendronate or risedronate , or have a contraindication to or are intolerant of alendronate and risedronate or have a contraindication to, or are intolerant of strontium ranelate (i.e. persistent nausea or diarrhoea)or who have had an unsatisfactory response to treatment with alendronate, risedronate and who are 65 years or older and have a T-score of 4.0 SD or below, or a T-score of 3.5 SD or below plus more than two fractures, or who are aged 5564 years and have a T-score of 4 SD or below plus more than two fractures. Patients suitable for treatment with Teriparatide should be referred to secondary care for confirmation of eligibility. Further investigation and treatment would be recommended in accordance with NICE guidance.

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4. Corticosteroid Induced Osteoporosis (CIOP) Corticosteroid therapy is one of the major risk factors for the development of osteoporosis and associated fractures. Approximately two thirds of patients on long term corticosteroids will develop significant osteoporosis but it is not possible to easily identify those at risk and, while it is generally true that bone loss is related to the dose and duration of treatment, this is by no means universal. It is generally accepted that the use of corticosteroids increases the risk of fracture between two to fourfold. Loss of BMD is greatest in the first few months of use. The distribution of fractures in patients receiving corticosteroid therapy is similar to post-menopausal osteoporosis. Scope of the Problem A community based study has suggested that 0.5% of the U.K. population are taking oral corticosteroids, and a hospital study has confirmed that 2% of medical outpatients are receiving long term corticosteroids (greater than 5 mg a day) with the highest frequency in patients with chronic obstructive airway disease and inflammatory arthritis. In general practice, 40 prescriptions for inhaled corticosteroids are written for every one prescription of oral therapy. There is some evidence that inhaled corticosteroids are associated with decreases in bone density but the overall effect is difficult to determine due to the compounding effects of previous oral corticosteroid therapy. Diagnosis A diagnosis of osteoporosis can be confirmed by measuring bone mineral density (BMD) by dual energy x-ray absorptiometry (DEXA) at the hip and lumbar spine sites. The WHO definition of osteoporosis is a BMD value of >2.5 SD below the mean for young adults of the same sex and race (T score -2.5). Repeat BMD measurements are also a valuable means of assessing the rate of bone loss or confirming a response to therapy. Current guidelines (CKS, 2009) recommend that those patients receiving corticosteroids with a T score below -1.5 should be considered for preventative therapy. General Measures Reduce dose if possible or steroid sparing agents Recommend good nutrition with adequate calcium and vitamin D Recommend regular weight bearing exercise Reduce alcohol and stop smoking Advice re reducing falls risk

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Corticosteroid Induced Osteoporosis (CIOP) Management Algorithm This algorithm is for patients taking, or anticipated to be taking oral glucocorticoids for 3 months or more. If there is a prevalent osteoporotic fracture, a diagnostic work-up is recommended and this should be performed before starting therapy. The tests that should be performed are to exclude myeloma, hyperparathyroidism, osteomalacia, malabsorption, thyrotoxicosis and hypogonadism.
Commitment or exposure to oral glucocorticoids for 3 months Age < 65 years Age 65 years

No previous fragility fracture

Previous fragility fracture or incident fracture during glucocorticoid therapy

Investigations

Measure BMD [DXA, hip spine]

T score above 0

T score between 0 and -1.5

T score -1.5 or lower** General measures Advice and treatment

Reassure General measures

General measures

Alendronate Calcitriol Risedronate

Repeat BMD not indicated unless very high dose of glucocorticoids required

Repeat BMD in 1-3 yr if glucocorticoids continued

The following are explanatory notes to the algorithm:

1

Investigations FBC, ESR Bone and liver function tests Serum creatinine Serum TSH If indicated Thoracic/lumbar spine X-rays Isotope bone scan Serum FSH Serum testosterone Serum PTH

**consider treatment depending on age and fracture probability Page 10 of 13

Treatment Options

The aim of the various treatment strategies is to limit bone loss and reduce fracture incidence. Whenever corticosteroid therapy is commenced patients should receive appropriate lifestyle advice about factors known to influence bone health. Doses of corticosteroid therapy should be kept under regular review and kept to the minimum necessary for disease control. Currently bisphosphonates (Alendronate and Risedronate) are the most effective agents for CIOP. In younger patients there is some uncertainty about the safety of long term bisphosphonate therapy and, for these patients, Calcitriol 0.25mcg BD may be a suitable alternative although serum calcium levels have to be monitored at regular intervals. There is currently little evidence to support the therapeutic use of vitamin D in either treatment or prevention but calcium and vitamin D supplements have a weak effect in secondary prevention. Monitoring and Follow-up For those patients on treatment in whom baseline BMD measurements have been undertaken, measurements of the lumbar spine and hip BMD after 1 year and then every 1-3 years, depending on the result, are recommended. If annual bone loss is greater than 4% at the spine and/or 7% at the hip: if not on treatment, osteoporosis therapy should be started; if on treatment, an alternative therapy should be considered and/or referral to a specialist.

5. Aromatase Inhibitor Guidelines Algorithms for bone loss in early breast cancer have been proposed and supported by the National Cancer Research Institute Breast Study Cancer Group and the National Osteoporosis Society and it is recommended that these are adopted for local implementation: Algorithm 1: deals with adjuvant treatment associated with ovarian suppression/ failure with or without concomitant aromatase inhibitor use in women who experience premature menopause. Algorithm 2: deals with postmenopausal adjuvant treatment with aromatase inhibitors.

6. Specialist Referral is recommended for

People less than 40 Males < 65 years with idiopathic osteoporosis Cases who continue to fracture while receiving treatment Assistance needed to confirm diagnosis Secondary osteoporosis - referral may be indicated Hyperparathyroidism or other endocrine diseases affecting bone Patients unable to comply with oral therapy who may be suitable for intra-venous bisphosphonate therapy (zoledronic acid) Patients unable to comply with oral therapy who may be suitable for subcutaneous therapy (denosumab) Patients unable to comply with oral therapy who may be suitable for Teriparatide (PTH) according to NICE TA 161. Cases eligible for either percutaneous vertebroplasty or balloon kyphoplasty for vertebral compression fractures in accordance with NICE IPG12 &IPG166

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7. References Clinical Knowledge Summaries (2009). Osteoporosis - Preventing Steroid-Induced. Accessed via www.cks.nhs.uk London New Drugs Group (2010). APC/DTC Briefing Document on Denosumab. London: London New Drugs Group Map of Medicine Health Guides (2010), Osteoporosis. Accessed via http://healthguides.mapofmedicine.com on Feb 1st 2011 National Institute for Clinical Excellence (2004). Falls: the assessment and prevention of falls in older people. Clinical Guideline 21.London: NICE. National Institute for Health & Clinical Excellence (2010).Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women (amended). TA160. London: NICE National Institute for Health & Clinical Excellence (2010).Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and Teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women (amended). TA161. London: NICE National Osteoporosis Guideline Group (NOGG). (2008).Guideline for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. London: NOGG. Accessed via www.shef.ac.uk/NOGG National Osteoporosis Society. Accessed via www.nos.org.uk Ralston H et al (2009).Women over 75 with fragility fractures should have DEXA.British Medical Journal; 338:b2340 Scottish Intercollegiate Guidelines Network (2003) Management of Osteoporosis: a National Clinical Guideline. SIGN Guidance 71.Edinburgh: SIGN

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8. Information Resources for Patients and Carers The National Osteoporosis Society provides excellent information on all aspects of osteoporosis for the public and health care professionals. These can be obtained from: National Osteoporosis Society Camerton, Bath, BA2 0PJ Tel: 01761 471771 or helpline: 0845 130 3076 (Mon to Thu 9.00am to 4.30 pm; Friday 9.00am to 4.00pm) www.nos.org.uk Email: info@nos.org.uk

In addition the following resources have been produced by organisations certified by The Information Standard: 'The Silent Disease (Osteoporosis)' (PDF) from Arthritis Care at http://www.arthritiscare.org.uk 'Osteoporosis - Looking after your bones' (PDF) from British Dietetic Association at http://www.bda.uk.com 'Vitamin D - The Unique Vitamin' (PDF) from British Dietetic Association at http://www.bda.uk.com 'Osteoporosis' (URL) from BUPA at http://www.bupa.co.uk/health_information/ 'Osteoporosis and diet' (URL) from BUPA at http://www.bupa.co.uk/health_information/ 'Osteoporosis' (URL) from Datapharm at http://www.medguides.medicines.org.uk 'Osteoporosis, osteomalacia and epilepsy' (URL) from Epilepsy Action at http://www.epilepsy.org.uk 'The bones and IBD' (PDF) from National Association for Colitis and Crohn's Disease at http://www.nacc.org.uk 'Understanding NICE guidance: Osteoporosis - primary prevention' (PDF) from National Institute for Health and Clinical Excellence (NICE) at http://www.nice.org.uk 'Osteoporosis' (URL) from Patient UK at http://www.patient.co.uk 'Preventing Steroid-induced Osteoporosis' (URL) from Patient UK at http://www.patient.co.uk Information for carers and people with disabilities is available at: 'Caring for someone' (URL) from Directgov at http://www.direct.gov.uk 'Disabled people' (URL) from Directgov at http://www.direct.gov.uk Patient stories describing their care journeys are available at Healthtalkonline' (URL) from DIPEx at http://www.healthtalkonline.org Explanations of clinical laboratory tests used in diagnosis and treatment are available at Understanding Your Tests (URL) from Lab Tests Online-UK at http://www.labtestsonline.org.uk

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