WAHT- TWI Guidelines for Osteoporosis in Worcestershire.

GUIDELINES FOR OSTEOPOROSIS IN WORCESTERSHIRE This guidance does not override the individual responsibility of health professionals to make appropriate decisions according to the circumstances of the individual patient in consultation with the patient and /or carer. Health care professionals must be prepared to justify any deviation from this guidance. INTRODUCTION 3 million people in UK have osteoporosis Almost half of the 10.6 million women aged over 50 in the UK will break a bone during their lifetime, mainly due to osteoporosis Only 480,000 women on bone fracture prevention 1 in 5 men will fracture a bone after the age of 50 A progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture (WHO 1994) i.e. a BMD T-score of -2.5 SD or below peak BMD (BMD for a young adult.) A skeletal disorder characterised by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength is dependent on Bone Density in g/cm 2 and bone architecture quality which is influenced by bone architecture, bone turnover and damage accumulation (NIH Consensus Development Panel on Osteoporosis JAMA 285 (2001) 785-95). (A 10-year risk of fracture model has been developed to identify those at highest risk. See guideline. (www.shef.ac.uk/frax)) More information is available on the Map of Medicine for Osteoporosis via the Worcestershire Health Libraries website: http://www.wkp.nhs.uk/specialist-services/projects/map-of-medicine.aspx THIS GUIDELINE IS FOR USE BY THE FOLLOWING STAFF GROUPS: All staff groups in primary and secondary care in Worcestershire involved in the treatment of patients with osteoporosis and osteoporotic fragility fracture(s) or at risk of developing osteoporosis or osteoporotic fragility fracture(s). Osteoporosis Specialist Nurse. See guideline for details of patient groups. Lead Clinicians Dr R Dutta Dr A Rai Mrs R Hodkinson Consultant Physician Elderly Care Consultant Physician Rheumatology Lead Clinical Pharmacist Trauma and Orthopaedics (WRH) Approved by Medicines Safety Committee on: 20 May 2008 Approved by Area Prescribing Committee on: Additional guidance approved for Denosumab 3 April 2012 2 August 2011 This guideline should not be used after end of: April 2014 Worcestershire Acute Hospitals NHS Trust Page 1 of 35

THIS DOCUMENT MUST NOT BE PHOTOCOPIED If you require a copy for your ward / department, please contact the Clinical Effectiveness Department on 01905 760717 PLEASE NOTE THAT ALL CLINICAL GUIDELINES / PROTOCOLS / POLICIES ARE ALSO AVAILABLE ON THE TRUST INTRANET Worcestershire Acute Hospitals NHS Trust Page 2 of 35

CONTENTS GUIDELINES FOR OSTEOPOROSIS FOR WORCESTERSHIRE.. 1 INTRODUCTION 1 To be used by the following staff groups 1 Lead clinicians. 1 Approval dates 1 Contents.. 3 Introduction... 5 Who to scan (including clinical risk factors)... 6 Treatment: life styles changes... 8 1 Lifestyle advice. 8 2 Assess the risk of falls. 8 3 Calcium and vitamin D 8 4 Exercises. 8 General principles of primary prevention of osteoporotic fragility fracture(s) in women...9 Treatment: Which drug... 10 - First-line.... 10 - Second-line... 10 - Third-line or if intolerant of bisphosphonates or contraindicated. 10 Secondary prevention/treatment of osteoporotic fragility fracture(s) in women..... 12 Treatment: Which drug... 12 - First-line.... 12 - Second-line... 12 - Third-line or if intolerant of bisphosphonates or contraindicated. 12 - Alternatives if both bisphosphonates and Strontium cannot be taken.13 Cautions, relative and absolute contraindications that affect choice of treatment 15 Other factors that affect choice of treatment...16 Men with osteoporosis... 17 Outcome measures... 20 Monitoring tool... 20 References... 21 Appendix 1 Breast cancer patients... 22 Appendix 2 Bowel disease patients... 23 Appendix 3 Corticosteroid therapy... 25 Appendix 4A Level 1 Falls Referral Form... 26 Appendix 4B Level 3 Specialist Falls Clinic Referral Form... 27 Appendix 5 DEXA scan request form... 29 Appendix 6 DEXA scan report letter..30 Appendix 7 Quick reference guide to primary prevention of Osteoporotic fragility fracture(s)in Women 31 Quick reference guide to secondary prevention of Osteoporotic fragility fracture(s) in Women. Quick reference guide to Osteoporosis in Men Quick reference guide to Osteoporosis in Breast cancer patients Quick reference guide to Osteoporosis in bowel disease patients Quick reference guide to Osteoporosis in corticosteroid patients..31 Appendix 8 Referral for Osteoporosis Specialist Nurse...32 Worcestershire Acute Hospitals NHS Trust Page 3 of 35

Appendix 9 Guidelines for initiating treatment with Denosumab.33 Contribution list....34 Worcestershire Acute Hospitals NHS Trust Page 4 of 35

GUIDELINES FOR OSTEOPOROSIS FOR WORCESTERSHIRE INTRODUCTION 3 million people in UK have osteoporosis Almost half of the 10.6 million women aged over 50 in the UK will break a bone during their lifetime, mainly due to osteoporosis Only 480,000 women on bone fracture prevention 1 in 5 men will fracture a bone after the age of 50 A progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture (WHO 1994) i.e. a Bone Mineral Density (BMD) 2.5 Standard Deviations (SD) or more below the young female adult mean (T-score of -2.5 or below). T- score relates to the measurement of bone mineral density (BMD) using central (hip and/or spine) dual-energy X-ray absorptiometry (DEXA) scanning. (NICE technology appraisal guidance 160 and 161, October 2008) A skeletal disorder characterised by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength is dependent on Bone Density in g/cm 2 and bone architecture quality which is influenced by bone architecture, bone turnover and damage accumulation (NIH Consensus Development Panel on Osteoporosis JAMA 285 (2001) 785-95). (A 10-year risk of fracture model has been developed to identify those at highest risk. The FRAX tool (www.shef.ac.uk/frax) computes the 10-year probability of hip fracture or a major osteoporotic fracture using a patient s clinical risk factors with or without bone mineral density results. This should be used in combination with a falls risk assessment. NICE are currently developing a guideline to assess the fracture risk). Worcestershire Acute Hospitals NHS Trust Page 5 of 35

GUIDELINE WHO TO DEXA SCAN? (Dual energy X-ray absorptiometry DEXA) A 10-year risk of fracture model has been developed to identify those at highest risk. The FRAX tool (www.shef.ac.uk/frax) computes the 10-year probability of hip fracture or a major osteoporotic fracture using a patient s clinical risk factors with or without bone mineral density (BMD) results, but see notes below. (NB the tool does not currently include falls in the algorithm and a falls risk assessment should also be carried out) The clinical risk factors (in combination with BMD results) used by the FRAX tool in computing the 10 year fracture risk are: Age Sex BMI Previous fracture Parent fractured hip Current smoking Glucocorticoids (equivalent to Prednisolone 5mg daily or more for more than 3 months) Rheumatoid arthritis Secondary osteoporosis (i.e. the patient has a disorder strongly associated with osteoporosis. These include type I (insulin dependent) diabetes), osteogenesis imperfect in adults, untreated long standing hyperthyroidism, hypogonadism or premature menopause (<45 years), chronic malnutrition, or malabsorption and chronic liver disease. Alcohol 3 or more units per day NICE are also developing a clinical guideline Osteoporosis: assessment of fracture risk and the prevention of osteoporosis fractures in individuals at high risk. Fracture risk should be assessed in postmenopausal women and in men aged 50 years or more: If using the FRAX model: - If using before a BMD is obtained and the patient has a fracture probability above the lower no treatment threshold but below the higher treatment threshold, a DEXA scan should be considered and the fracture risk reassessed once the BMD is known. - If using before a BMD is obtained and the probability obtained is below the lower assessment threshold, the patient can be reassured and reassessed as their clinical risk factors change. - If using before a BMD is obtained and the probability is above the intervention threshold, treatment should be considered without the need for a DEXA scan, although it may be useful to monitor response. If not using the FRAX model, identify patients at risk using definitions provided in NICE TA160 and NICE TA161: Table 1 Indicators of low BMD (column A) Independent clinical risk factors for fracture (column B) Low body mass index (BMI 22kg/m 2 or less) Rheumatoid Arthritis Untreated premature menopause Parental history of hip fracture Prolonged Immobilisation Alcohol intake of 4 units or more daily Ankylosing spondylitis Crohn s disease (see appendix 2) Then for women: Worcestershire Acute Hospitals NHS Trust Page 6 of 35

Table 2 Age Risk factors (from table 1) DEXA scan? 75 or older 2 or more Not if clinically inappropriate or unfeasible 65-74 1 or more Yes Under 65 years old 2 or more (1 each from Yes columns A&B) In men men are not currently covered in the NICE guidelines but NOGG (www.shef.ac.uk/nogg/) have issued guidelines which include men over the age of 50 see page 16. In addition the following clinical risk factors either increase fracture risk independently of BMD or are associated with low BMD and are therefore secondary causes of osteoporosis and in patients with these risk factors, clinicians will need to assess on a case by case basis who should be referred for a scan (e.g. patients also at risk of falls): Low trauma fracture or vertebral deformity, age less than 75 years Oral steroid therapy, age less than 65 years (see appendix 3) Men and women with primary hypogonadism Premature menopause (age less than 45 years) or prolonged amenorrhoea Untreated menopause Radiographic evidence of osteopenia Chronic disease associated with osteoporosis: - Anorexia Nervosa - Malabsorption - Primary Hyperparathyroidism - Post-transplantation - Chronic Renal Failure - Hyperthyroidism - Cushing s Syndrome Post menopausal women with maternal hip fracture or body mass index (BMI) 19kg/m² or less Other Clinical risk factors to consider: Type I diabetics. Current smokers. Reversible secondary causes of osteoporosis, such as those listed above, should be excluded, in both men and women, before treatment for osteoporosis is initiated. Monitoring therapy In the initial stages of osteoporosis treatment a repeat DEXA scan at 18-24 months may be considered to assess response, depending on the clinical picture and fracture risk. Worcestershire Acute Hospitals NHS Trust Page 7 of 35

ALL PATIENTS Treatment: life styles changes 1. Lifestyle advice diet, stopping smoking and reducing alcohol intake. 2. Assess the risk of falls, particularly in the elderly [Age/Polypharmacy/Cognitive impairment/lack of exercise/vitamin D deficiency]. Refer all patients to the Community Falls Co-ordinator using the Level 1 referral form for a community falls assessment. (See appendix 4a). For complex patients or those with unexplained recurrent falls, use the Level 3 referral form (appendix 4B) to refer to the specialist hospital falls clinic. 3. Calcium and Vitamin D 3 Ensure a daily intake of at least 1g calcium and 800 IU vitamin D daily. Check serum calcium, alkaline phosphatase and occasionally Vitamin D levels (10-60 ng/ml) first. If dietary intake is inadequate, prescribe in a suitable combination preparation. (There is now a range of formulations available to aid compliance and patient tolerability.) Consider Calcium and Vitamin D supplementation in housebound (e.g. care homes), frail, elderly patients at risk of falls. See Guidelines for the use of calcium and vitamin D in falls prevention in adults. Worcestershire County Area Prescribing Committee. The use of anti-resorptive agents e.g. Bisphosphonates, Strontium and Denosumab are contraindicated in patients with hypocalcaemia, therefore ensure any deficiency is corrected before initiating therapy with these agents. 4. Exercises: Bones, like muscles, become weaker if not exercised. Regular weight bearing exercise can improve bone density and reduce fracture risk. (Wolf I, 1999). Exercise can also improve balance and co-ordination, strength and flexibility all of which decrease the risk of falls and hence the risk of fracture. Because of the varying degrees of osteoporosis and the risk of fracture certain flexibility exercises, strength training and weight bearing aerobic exercise may be unsuitable. Three types of exercise are recommended (CSP, 2001): 1) Flexibility exercises such as stretching to improve posture (Kelley G, 1998). These can help to reduce harmful stress on bones and maintain bone density. 2) Strength training including resistance training with weights (Kerr D, 1996). To be most effective these should be site specific, of sufficient intensity, progressive and low repetition. 3) Weight bearing aerobic exercises (Bassey EJ, 1995). Generally, in pre-menopausal women without a diagnosis of osteoporosis high impact exercise such as skipping, jogging and jumping has the greatest potential to improve BMD. For those not used to exercising and those over 50 years of age, low to medium impact exercise, such as step aerobics, intermittent jogging, brisk walking is more appropriate. In those patients with a diagnosis of osteoporosis stair climbing, low impact aerobics, line dancing, and Tai Chi will improve balance and strength. High impact exercises, high impact aerobics, sharp reflex actions e.g. squash, badminton and exercise which involves excessive forward bending should be avoided. These activities increase compression in the spine and lower extremities and can lead to fractures in weakened bones. Swimming and cycling are non-weight bearing exercises and therefore do not increase bone density. However, they improve fitness levels and joint mobility which allows weight bearing exercises to be performed more effectively. Worcestershire Acute Hospitals NHS Trust Page 8 of 35

GENERAL PRINCIPALS OF PRIMARY PREVENTION OF OSTEOPOROTIC FRAGILITY FRACTURES IN WOMEN 1. Follow the guidelines on page 6 Who to DEXA scan 2. Post-menopausal women fracture more in later years, independent of BMD values. This makes them more vulnerable to fracture from falling, particularly if they have recurrent falls. 3. Avoid treating young worried well (e.g. osteopenia) who have a low fracture probability as assessed by FRAX score use the FRAX tool (www.shef.ac.uk/frax). 4. Borderline osteoporosis in the young needs to have their secondary causes identified and treated and consider referring to Secondary care. 5. Bisphosphonates are teratogenic and use in pre-menopausal women should be given with caution and counselling. 6. Bisphosphonates are licensed for use in men and women as a daily preparation. However, weekly preparations may be prescribed on an off-label use to improve compliance. 7. Osteopenic patients can be helped with life-style changes, unless 10 year fracture risk is high otherwise use the FRAX tool (www.shef.ac.uk/frax). 8. If results OSTEOPOROTIC, discuss drug management, see table 3 below. 9. Advise that once treatment for osteoporosis is started it is likely that this will need to be continued. Table 3 Age Risk factors (see DEXA Scan result table 1 on page 6) (T score) 75 or older 2 or more (A or B) Not necessarily needed if scan unfeasible or not thought clinically appropriate. Action Drug treatment page 10 70 or older 1 or more (A or B) - 2.5 or below Drug treatment page 10 65 69 1 or more (1 must be from column B) - 2.5 or below Drug treatment page 10 Under 65 years 2 or more (1 each from columns A&B) - 2.5 or below Drug treatment page 10 Worcestershire Acute Hospitals NHS Trust Page 9 of 35

TREATMENT: DRUG THERAPIES PRIMARY PREVENTION OF OSTEOPOROTIC FRAGILITY FRACTURES IN WOMEN (Drug therapy to prevent fragility fractures in at risk patients) The FRAX tool (www.shef.ac.uk/frax) can also help identify patients at high risk of fractures who should be given drug therapy to prevent fragility fractures. As discussed above (Who to DEXA scan? page 5) See clinical risk factors above, when identifying patients at a high risk of fractures. WHICH DRUG: First line: -Generic oral alendronate 10mg daily Consider prescribing 70mg once weekly preparation to encourage compliance (although not licensed for primary prevention) Second-line: -Risedronate orally 5mg daily. (Consider using 35mg once weekly to encourage compliance although not licensed for primary prevention) -Disodium etidronate orally as Didronel PMO These should be used when the patient has a contraindication to or intolerance of Alendronate or be unable to comply with the special instructions for its administration (See What factors affect choice of treatment? On page 14) AND also have a combination of T-Score, age and number of independent clinical risk factors as shown in the following table: Table 4 Number of independent clinical risk factors (Table 1 column B) Age 0 1 2 65-69 X -3.5-3.0 70-74 -3.5-3.0-2.5 75 or older -3.0-3.0-2.5 (X - treatment with Risedronate or Etidronate is not recommended) Third-line or if intolerant of bisphosphonates or contra-indicated : Strontium ranelate OR Denosumab: Strontium or Denosumab should be used when the patient has a contraindication to or intolerance of bisphosphonates or are unable to comply with the special instructions for their administration (See What factors affect choice of treatment? On page 16) AND also have a combination of T-Score, age and number of independent clinical risk factors as shown in the following table: Table 5 Number of independent clinical risk factors (Table 1 column B) Age 0 1 2 65-69 X -4.5-4.0 70-74 -4.5-4.0-3.5 75 or older -4.0-4.0-3.0 (X treatment with Strontium or Denosumab is not recommended) -Strontium ranelate 2g sachet at night. Falsely increases bone density, up to 50%, hence BMD reading subsequently not reliable. Current NICE guidelines (TA160 October 2008) recommend Strontium as a treatment option for the primary prevention of osteoporotic fractures in postmenopausal women at increased risk of fractures in the circumstances above. Worcestershire Acute Hospitals NHS Trust Page 10 of 35

-Denosumab Injection 60mg administered as a single subcutaneous injection once every 6 months into the thigh, abdomen or back of arm. Denosumab is a human monoclonal IgG2 antibody produced in a mammalian cell line by recombinant DNA technology. Current NICE guidelines (TA204 October 2010) recommend Denosumab as a treatment option for the primary prevention of osteoporotic fractures in postmenopausal women at increased risk of fractures in the circumstances above. See also Worcestershire Area Prescribing Committee. Guidelines for initiating treatment with Denosumab. August 2011. http://www.worcestershire.nhs.uk/file_download.aspx?id=36775554-a556-4dd4-b377-6daf5f880735 See Appendix 9. Worcestershire Acute Hospitals NHS Trust Page 11 of 35

SECONDARY TREATMENT/PREVENTION OF OSTEOPOROTIC FRAGILITY FRACTURES IN WOMEN Guidance for secondary prevention of fragility fractures in postmenopausal women who have osteoporosis and have sustained a clinically apparent osteoporotic fragility fracture. Table 6 Age DEXA Scan result Action (T score) 75 or older Not needed Drug treatment see below Under 75-2.5 or below Drug treatment see below Notes Age 75 years or older, no need for prior DEXA scanning if clinician considers clinically inappropriate or unfeasible. Women who have had 2+ vertebral fractures treatment may be started while waiting for a DEXA scan. The National Orthopaedic Guideline Group (NOGG) recommend that women with a prior fragility fracture should be considered for treatment without the need for further risk assessment, although BMD measurement may sometimes be appropriate, particularly in younger postmenopausal women. www.shef.ac.uk/nogg/. This may result in more women receiving treatment than what NICE guidelines recommend and each case should be considered using all assessment models available and a decision reached between patient and clinician. Further advice is available from the Rheumatologists, Care of the Elderly team, Endocrinologists or Osteoporosis specialist nurse (appendix 8 referral form) in secondary care. Please see appendices 1, 2 and 3 for other patient groups. Osteoporotic fragility fracture is a fracture sustained as a result of a force equivalent to the force of a fall from a height equal to, or less than, that of an ordinary chair. WHICH DRUG: First-line - Generic oral alendronate 70mg weekly. (10mg daily licensed for osteoporosis in men, 5mg daily licensed for treatment of corticosteroid induced osteoporosis, 10mg daily licensed for corticosteroid induced osteoporosis in postmenopausal women not taking HRT however prescribers may wish to consider 70mg weekly preparation for off-license use on a named patient basis to improve patient compliance.) Second-line -Risedronate orally 35mg weekly. -Disodium etidronate orally as Didronel PMO Recommended as alternative treatment when the patient cannot comply with the special instructions for the administration of Alendronate or have a contraindication to or are intolerant of Alendronate. Third-line or if intolerant of bisphosphonates or contra-indicated : - Strontium ranelate orally or Denosumab injection -Strontium ranelate 2g sachet at night. Falsely increases bone density, up to 50%, hence BMD reading subsequently not reliable. Strontium should be used when the patient has a contraindication to or intolerance of bisphosphonates or is unable to comply with the special instructions for their administration (See What factors affect choice of treatment? On page 16), or in women who have had an unsatisfactory response to bisphosphonates defined as when the patient has had another fragility fracture despite adhering fully to treatment Worcestershire Acute Hospitals NHS Trust Page 12 of 35

for 1 year and there is evidence of a decline in BMD below their pre-treatment baseline if measured AND also have a combination of T-Score, age and number of independent clinical risk factors as shown in the following table: Table 7 Number of independent clinical risk factors (Table 1 column B) Age 0 1 2 50-54 X -3.5-3.5 55-59 -4.0-3.5-3.5 60-64 -4.0-3.5-3.5 65-69 -4.0-3.5-3.0 70-74 -3.0-3.0-2.5 75 or older -3.0-2.5-2.5 (X treatment with Strontium is not recommended) Patients should advised to stop treatment if a skin rash occurs as this can be the first sign of a severe allergic reaction (DRESS see BNF or product literature http://emc.medicines.org.uk/ - Denosumab 60mg Injection administered as a single subcutaneous injection once every 6 months into the thigh, abdomen or back of arm. Denosumab is a human monoclonal IgG2 antibody produced in a mammalian cell line by recombinant DNA technology. Denosumab should only be considered as a treatment option in patients who are unable to comply with the special instructions for administering Bisphosphonates, or have an intolerance of, or a contraindication to Bisphosphonates. See also Worcestershire Area Prescribing Committee. Guidelines for initiating treatment with Denosumab. August 2011. http://www.worcestershire.nhs.uk/file_download.aspx?id=36775554-a556-4dd4-b377-6daf5f880735 See Appendix 9. If both bisphosphonates, strontium ranelate and denosumab cannot be taken, alternatives are: Raloxifene 60mg Daily Teriparatide - 20micrograms once daily by subcutaneous injection for a maximum of 18 months. - Should be initiated and prescribed by specialists. - Should only be considered if patients who: Are unable to take a bisphosphonate (e.g.poor compliance, intolerance, contraindication.) Have a contraindication to, or are intolerant of Strontium. Have had an unsatisfactory response to bisphosphonates or Strontium (defined when a patient has another fragility fracture despite adhering fully to treatment for 1 year and there is evidence of a decline in BMD below their pre-treatment baseline.) Worcestershire Acute Hospitals NHS Trust Page 13 of 35

And: Table 8 Age N o fractures DEXA scan result (T-score) Action 65 or older 1-4.0 or below Consider Teriparatide 65 or older 2+ - 3.5 or below Consider Teriparatide 55-64 2+ - 4.0 or below Consider Teriparatide Intranasal calcitonin. (Licensed for the treatment of postmenopausal osteoporosis to reduce risk of vertebral fractures.) Hormone replacement therapy-hrt. The CSM has advised that HRT should not be considered first-line therapy for the long-term prevention of osteoporosis in women over 50 years of age. HRT is of most benefit for the prophylaxis of postmenopausal osteoporosis if started early in menopause and continued for up to 5 years, but bone loss resumes (possibly at an accelerated rate) on stopping HRT. It should only be considered if other therapies are contraindicated, cannot be tolerated, or if there is a lack of response. Discuss the risks versus benefits before prescribing (for prescriptions see the CKS topic on Menopause). More information on cautions, contraindications and side-effects can be found in the current BNF. Worcestershire Acute Hospitals NHS Trust Page 14 of 35

Cautions, relative and absolute contraindications that affect choice of treatment: This list is not exhaustive and prescribers should ensure they are aware of specific cautions and contraindications for each drug they prescribe. Information can be found in the current BNF which can be accessed via http://www.bnf.org or in the manufacturers summaries of product characteristics which can be accessed via http://emc.medicines.org.uk/ Oesophageal stricture or achalasia / current or recent history of other upper gastrointestinal disorders: Do not use alendronate, try risedronate (but monitor closely for adverse effects). Oesophageal reactions: Severe oesophageal reactions have been reported with all oral bisphosphonates: patients should be advised to stop tablets and seek medical attention for symptoms of oesophageal irritation such as dysphagia, pain on swallowing, retrosternal pain or heartburn. Other contraindications for bisphosphonates are: o o o Pregnancy, breast feeding. Hypocalcaemia must be corrected before starting treatment and then serum calcium concentrations monitored during treatment. Severe renal impairment (see paragraph below) When using bisphosphonates, balance the drug s overall proven effectiveness profile against tolerability and adverse effects in individual patients. NOGG have produced a tabular guide showing the main drug therapies evaluated effect on fracture risk. www.shef.ac.uk/nogg/ Venous thrombosis (active or past history): avoid raloxifene, strontium ranelate and hormone replacement therapy. Endometrial cancer, unexplained vaginal bleeding, or breast cancer: do not use raloxifene or hormone replacement therapy. Osteonecrosis of the jaw: Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including bisphosphonates administered intravenously or Denosumab injection. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates. A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates and Denosumab in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene). This should be carried out in Primary Care. While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate or Denosumab therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw but the bisphosphonates have long half-lives in bone which may suggest that discontinuation will have no added value. (www.bnf.org.uk) (http://emc.medicines.org.uk/) Severe renal impairment: Obtain specialist advice from a renal specialist team if appropriate. Current advice regarding suitability and dosing in patients with renal Worcestershire Acute Hospitals NHS Trust Page 15 of 35

impairment can be found in the current BNF (www.bnf.org.uk) or in the manufacturer s summaries of product characteristics. (http://emc.medicines.org.uk/) - Alendronate Avoid if egfr less than 35ml/min/1.73m 2 - Risedronate Avoid if egfr less than 30ml/min/1.73m 2 - Etidronate Avoid if egfr less than 20ml/min/1.73m 2 - Raloxifene Avoid if egfr less than 10ml/min/1.73m 2 - Strontium Avoid if egfr less than 30ml/min/1.73m 2 - Denosumab greater risk of developing hypocalcaemia if CrCl less than 30ml/min or receiving dialysis. Manufacturers advise monitoring plasma calcium concentrations. Other factors that affect choice of treatment: Compliance: Bisphosphonates have very specific administration requirements (see counselling points under each drug in the current BNF). Prescribers must ensure that the patient will comply with these instructions. Weekly preparations may increase compliance with some patients. Special consideration needs to be given to patients who have drugs administered by carers, especially on home visits, as they may not be able to supervise the patient for an adequate amount of time to ensure all the counselling points are followed. An unsatisfactory response = another fragility fracture despite adhering fully to treatment for 1 year and there is also evidence of a decline in BMD below her pretreatment baseline. Intolerance of oral bisphosphonates is defined as persistant 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. (NICE TA161) Intolerance of Strontium ranelate is defined as persistent nausea or diarrhoea, either of which warrants discontinuation of treatment. (NICE TA161) Worcestershire Acute Hospitals NHS Trust Page 16 of 35

MEN WITH OSTEOPOROSIS Not currently covered by NICE guidelines. NOGG have produced guidelines for men over the age of 50. (www.shef.ac.uk/nogg/) What: Lifestyle advice on dietary calcium and vitamin D intake, exercise, stopping smoking and reducing alcohol intake. (see also section above page 8) Assess the risk of falls, particularly in the elderly. All men should be investigated for hypogonadism. Exclude secondary causes of osteoporosis by performing the following investigations: o Testosterone, gonadotrophins (FSH, LH, and SHBG) to exclude hypogonadism o FBC, ESR, CRP o If ESR raised, check serum and urine electrophoresis to exclude multiple myeloma o o o o Bone, liver, and renal biochemistry, to exclude osteomalacia, other metabolic causes of osteoporosis, and renal osteodystrophy TFTs, to exclude hyperthyroidism Bone profile including calcium, alkaline phosphate and vitamin D3 levels Men on LHRH analogues treatment for prostatic cancers. A 10-year risk of fracture model has been developed to identify those at highest risk. The FRAX tool (www.shef.ac.uk/frax) computes the 10-year probability of hip fracture or a major osteoporotic fracture using a patient s clinical risk factors with or without bone mineral density results. (Nb the tool does not currently include falls in the algorithm and a falls risk assessment should also be carried out) o o If access is available to use the FRAX model, follow their assessment tool for each individual patient. If access to the FRAX model is not available, the following algorithm from the NOGG guidelines can be used: The charts below give average 10 year fracture probabilities according to age, BMI and the number of risk factors. The chart is colour coded. Green denotes that an individual s risk lies below the intervention threshold i.e. treatment is not indicated. Red denotes that the fracture probability is consistently above the upper assessment threshold, irrespective of the mix of risk factors, so that treatment can generally be strongly recommended. The intermediate category (yellow) denotes that probabilities lie between these limits and that a BMD test should be considered to improve the estimate of fracture risk. Assessment of men with or without previous fracture according to body mass index (BMI) and the number of risk factors (as shown in table 1) Table 1 (modified for men) Indicators of low BMD (column A) Independent clinical risk factors for fracture (column B) Low body mass index (BMI 22kg/m 2 or less) Rheumatoid Arthritis Parental history of hip fracture Prolonged Immobilisation Alcohol intake of 4 units or more daily Ankylosing spondylitis Crohn s disease (see appendix 2) Worcestershire Acute Hospitals NHS Trust Page 17 of 35

Age 50 N o risk factors (as in table 1) 1 4.5 4.3 4.3 3.7 3.3 2 7.1 6.7 6.5 5.7 4.9 3 11 10 9.7 8.5 7.4 BMI 15 20 25 30 35 Age 60 N o risk factors (as in table 1) 1 6.5 6.1 6.0 5.2 4.5 2 10 9.3 8.9 7.7 6.7 3 15 14 13 11 9.9 BMI 15 20 25 30 35 Age 70 N o risk factors (as in table 1) 1 9.0 8.5 8.2 6.9 5.9 2 13 12 12 9.9 8.4 3 20 18 17 14 12 BMI 15 20 25 30 35 Age 80 N o risk factors (as in table 1) 1 12 11 11 8.7 7.1 2 19 17 16 13 10 3 27 25 23 19 15 BMI 15 20 25 30 35 Reassure. Advise lifestyle changes Consider DEXA scan Consider treatment +/- DEXA scan If/when DEXA scan results are available: In men in whom BMD is available at the femoral neck, 10 year fracture probability can be approximated according to age, BMD T-score and the number of risk factors. The chart below is colour coded. Green denotes that an individual s risk lies below the intervention threshold i.e. treatment is not indicated. Red denotes that the fracture probability is consistently above the upper assessment threshold, irrespective of the mix of risk factors, so that treatment can be strongly recommended in most cases. The intermediate category (yellow) denotes that probabilities lie between these limits and that treatment can be recommended in those with the stronger risk factors. Assessment of men with or without previous fracture according to femoral neck T- score for BMD and risk factors as shown in table 1 Table 1 (modified for men) Indicators of low BMD (column A) Independent clinical risk factors for fracture (column B) Low body mass index (BMI 22kg/m 2 or less) Prolonged Immobilisation Ankylosing spondylitis Crohn s disease (see appendix 2) Rheumatoid Arthritis Parental history of hip fracture Alcohol intake of 4 units or more daily Worcestershire Acute Hospitals NHS Trust Page 18 of 35

Age 50 N o risk factors (as in table 1) 1 30 14 7.5 5.1 4.0 2 43 20 11 7.5 5.9 3 57 29 16 11 8.4 BMD - 4-3 - 2-1 0 Age 60 N o risk factors (as in table 1) 1 31 16 9.6 6.4 5.0 2 41 23 14 9.2 7.1 3 53 31 19 13 10 BMD - 4-3 - 2-1 0 Age 70 N o risk factors (as in table 1) 1 28 17 11 7.2 5.6 2 37 24 15 9.9 7.5 3 48 32 20 13 10 BMD - 4-3 - 2-1 0 Age 80 N o risk factors (as in table 1) 1 12 11 11 8.7 7.1 2 19 17 16 13 10 3 27 25 23 19 15 BMI - 4-3 - 2-1 0 Reassure. Advise lifestyle changes Consider treatment Strongly recommend treatment Consider referring all men with osteoporosis for specialist assessment and advice on treatment. Treatment in men is best initiated after specialist assessment. However, if there is likely to be considerable delay before seeing a specialist, it may be appropriate to start drug treatment. Treat with Alendronate and give calcium + vitamin D if dietary intake is low. Seek specialist advice for other treatment options if Alendronate is contraindicated or not tolerated. Bisphosphonates are licensed in men consider weekly preparations to improve compliance as above. Drug therapies licensed for use in men are: o o Alendronate Risedronate See above for usual doses used (page 10) Worcestershire Acute Hospitals NHS Trust Page 19 of 35

OUTCOME MEASURES following treatment for osteoporosis: Reduction in the number of fractures, particularly vertebral, hip, and other axial skeleton fractures. Reduction in the number of deaths following fractured femur. The proportion of people with a history of osteoporotic fragility fracture who are taking bone-protective treatment. MONITORING TOOL How will monitoring be carried out? Who will monitor compliance with the guideline? Clinical audit Secondary care pharmacy department, reporting to Medicines Safety Committee. (to monitor prescribing compliance) Clinical Governance primary and secondary care. Other groups as deemed appropriate. Standards as detailed in NICE guidance. Worcestershire Acute Hospitals NHS Trust Page 20 of 35

REFERENCES NICE TA87 Technology Appraisal Guidance 87 Bisophosphonates, selective oestrogen receptor modulators and parathyroid hormone for the second prevention of osteoporosis fragility fractures in postmenopausal women, January 2005. NOTE Now re-appraised as NICE TA161 see below. NICE TA160 technology appraisal guidance 160. Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women. October 2008. www.nice.org.uk/ta160 NICE TA161 technology appraisal guidance 161. Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women. October 2008. www.nice.org.uk/ta160 Hillner et al. Clin Oncol 2003 ; 21 :4042-57 BSG Guidelines for osteoporosis in inflammatory bowel disease and 2007. eliac disease June Clinical Knowledge Summaries Service (CKS) guidelines Guideline for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. National Osteoporosis Guideline Group. www.shef.ac.uk/nogg/ (accessed 20/11/08) FRAX tool for the assessment of fracture risk. National Osteoporosis Guideline Group. www.shef.ac.uk/frax (accessed 20/11/08 ) British National Formulary (BNF). Number 61. Published by BMJ group and RPS publishing, Bedfordshire, UK. March 2011. (www.bnf.org.uk) http://www.emc.medicines.org.uk/ accessed 6/09/2011 Worcestershire Area Prescribing Committee. Guidelines for initiating treatment with Denosumab. August 2011. http://www.worcestershire.nhs.uk/file_download.aspx?id=36775554-a556-4dd4-b377-6daf5f880735 NICE TA204 Technology Appraisal Guidance 204.Denosumab for the prevention of osteoporotic fractures in postmenopausal women. October 2010. www.nice.org.uk/ta204 Worcestershire County Area Prescribing Committee. Guidelines for the use of calcium and vitamin D in falls prevention in adults. April 2012 Worcestershire Acute Hospitals NHS Trust Page 21 of 35

APPENDIX 1 BREAST CANCER PATIENTS Breast Cancer Patients EFFECT OF TAMOXIFEN ON BONES: Pre-menopausal women: Post-menopausal women: Hip and Spine BMD No fractures in chemo-prevention trials BMD Hip and Spine at 1 year BMD at both sites at 3 years (about 4%) fracture-risk in chemo-prevention trials EFFECT OF AROMATASE-INHIBITORS ON BONES: Pre-menopausal women: Post-menopausal women: Prevents peripheral aromatization of androgen oestradiol. Not used in premenopausal women fracture-risk with anastrozole and letrozole. Exemestane BMD loss at hip and spine SUGGESTED MANAGEMENT: Low Risk: High Risk: Life style changes Calcium and Vitamin D supplements Monitor ANNUALLY for risk status CLINICALLY 65 years of age or older Aromatase therapy Women changing from Tamoxifen to Aromatase therapy Women undergoing Chemotherapy When the RESULTS are: Do BASELINE DEXA for hip and spine 1. NORMAL Suggest life-style changes; Calcium + Vitamin D 3-yearly DEXA scans 2. OSTEOPENIA As above, EXCEPT when Aromatase Therapy started commence Bisphosphonates 3. OSTEOPOROSIS Suggest life-style changes; Calcium + Vitamin D Bisphosphonates (NB Teratogenic properties) OR Raloxifene (but NOT when Aromatase Therapy in progress) ANNUAL DEXA scans. (Ref: from Hillner et al. Clin Oncol 2003; 21:4042-57) Worcestershire Acute Hospitals NHS Trust Page 22 of 35

APPENDIX 2 BOWEL DISEASE PATIENTS Inflammatory Bowel and Coeliac Disease Inflammatory Bowel Disease and Coeliac Disease are associated with increased risk of osteoporosis. Relative risk for all fractures is: 1:1.3 for Crohn s Disease 1:1.2 for Ulcerative Colitis 1:1.4 for Coeliac Disease General Recommendations Regular weight bearing exercise Balanced diet Dietary calcium intake ( up to 1200 mg daily) Treat Vitamin D deficiency ( Check ALP, Calcium and PTH) Avoid excess alcohol and smoking. Specific Measures for Inflammatory Bowel Disease Consider elemental or polymeric diet for Crohn s disease before steroids Early use of azathioprine / 6 MP. Steroid avoidance Consider budesonide instead of prednisolone for small bowel or ileo-caecal Crohn s disease. Budesonide is a glucocorticosteroid with a high local antiinflammatory effect. At doses clinically equivalent to systemically acting glucocorticosteroids, budesonide gives significantly less HPA axis suppression. It causes fewer systemic side-effects than oral prednisolone but may be less effective.( www.emc.medicines.org.uk www.bnf.org.uk ) Use steroids at the lowest effective dose and shortest effective duration Consider biological treatment if steroid remission is not achieved. For those on steroids: Age 65 or older: consider bisphosphonates on starting steroids Age under 65 years old: at high risk and requiring steroids (any dose) more than 3 months: DEXA and consider bisphosophonates if T score < -1.5 SD Give Vitamin D and Calcium DEXA Scan for those at higher risk of osteoporosis e.g. 2 or more of Continuing active disease Age 70 years or older Weight loss of more than 10% BMI less than 20 Specific Measures for Coeliac Disease General recommendations as above. DEXA scan for those at high risk Gluten-free diet Indications for DEXA Scan Persisting symptoms on gluten free diet for 1 year weight loss more than 10 % BMI less than 20 Age 70 or older Treatment of osteoporosis (see also notes in main guideline) Worcestershire Acute Hospitals NHS Trust Page 23 of 35

If low T score on DEXA + risk factors OR prior fragility fracture: Oral bisphosphonates, long term Intolerance or failure of bisphosphonates in postmenopausal women or men over 55 consider: Raloxifene ( only) Teriparatide daily injection for 18 months Calcitonin by intranasal spray Men with low BMD: Consider hypogonadism check blood testosterone and replace if low. Follow up DEXA scans For high risk patients on high dose steroid therapy Repeat DEXA for every subsequent year of steroid use until intervention threshold (T score of -1.5 is reached). Reference: BSG Guidelines for osteoporosis in inflammatory bowel disease and Coeliac disease June 2007. Worcestershire Acute Hospitals NHS Trust Page 24 of 35

APPENDIX 3 CORTICOSTEROID THERAPY CORTICOSTEROID THERAPY (Based on Clinical Knowledge Summaries Service (CKS) guidelines) Rate of corticosteroid use - 1% adult population to 2.4% (age 70-79 years) Corticosteroids cause significant fracture risk to hips and spines. Fractures seen at doses less than 7.5mg/day. High-dose inhaled steroids may also cause bone loss in some, as can low-dose chronic therapy. The greatest rate of bone loss occurs during the first 6-12 months of corticosteroid. Effect of corticosteroids tends to increase fracture-risk greater than with just the falling BMD. Risk of fracture is enhanced in this group. Fracture-risk assessment in this group recommended, using DEXA scanning. Recommended measures are: 1. Reduce dose of corticosteroids, where possible. 2. Consider use of alternative formulations. 3. Consider alternative immune-suppressive agents. 4. Encourage good nutrition, adequate calcium intake and physical activity. 5. Suggest tobacco and alcohol abuse reduction. Studies show beneficial effects on BMD with medications. REDUCTION IN VERTEBRAL FRACTURES observed during safety analysis on most of present-day bisphosphonates in use. TREATMENT OF STEROID-INDUCED OSTEOPOROSIS High-risk groups on corticosteroid therapy are: 1. 65 years old or older 2. Age 40 years or older, with previous fragility fractures (CAUTION: bisphosphonates teratogenic) - COMMENCE bone protection regime at the time of starting corticosteroids. For OTHERS: Appendix 5 - DEXA scan when corticosteroids to be used for more than 3 months (Consider commencing treatment when T score -1.5 SD or less). - Consider repeat DEXA 2 years after therapy commenced to check BMD. Worcestershire Acute Hospitals NHS Trust Page 25 of 35

APPENDIX 4A LEVEL 1 REFERRAL FORM FALLS ASSESSMENT (SEE NEXT PAGE) Worcestershire Acute Hospitals NHS Trust Page 26 of 35

FALLS RISK CASE FINDING TOOL Level 1 Level 1 Falls screening to be performed by any Health, Mental Health Team, Adult Community Services, Home Care Teams, A&E, MIU,Ambulance staff and Voluntary or Independent Sector setting. (Tool based on the falls risk assessment Tool - FRAT and has been adapted for local use) Name: Date of Birth NHS No. (if known): Address: Phone Number: Carer Contact Details / first point of contact if appropriate GP and Surgery: Name: Telephone: Please use, Guidance Notes and Agreed Action Plan overleaf before completing this form YES 1 Is there a history of any fall in the previous year? Number of falls in past 12 months. Approximate date of last fall 2 Is the person on four or more different medications per day? Has the person had a recent change in medication? - please circle: yes or no Has the person had a recent medication review? - please circle: yes or no Which chemist do you get your medicines from? - insert details in comments box below 3 Does the person have a diagnosis of stroke or Parkinson s disease? 4 Does the person have any problems with their balance? 5 Is the person unable to stand up from a chair of knee height without pushing up with their arms and hands? NO If the person has fallen, do they complain of blackouts, loss of consciousness? CONSENT: I am willing to have a further falls risk assessment if necessary. This may involve a referral to another member of the health care team. Verbal consent gained Yes No The details of this assessment will be added to the Central Falls Register held by the PCT. Verbal consent gained Yes No The assessor will give Falls Prevention advice and provide general Falls and Health and Well Being information. Tick Leaflet given 6. Comments: eg: form completed with carer. If form completed by OT/PT please circle OT /PT Assessment completed and intervention actioned Send all Level 1 screening tools to: Falls Prevention Coordinator: Training and Development Centre,Evesham Community Hospital, Waterside WR11 1JT TEL No 01386 502339/502486 FAX no 01386 502503 Email: wor-pct.falls-prevention@nhs.net Name of Assessor: Designation: Organisation: Signature: Date: Tel: Fallslevelonecasefindingtoolrevised April 2011

Guidance notes to assist completing the stage 1 screening tool 1. How assessed? Ask the person/carer if they have fallen in the last twelve months and the number of falls in the last twelve months (please note the number of falls in the space provided) If the person had 1 or more falls in the last twelve months, place a tick in the YES column. 2. How assessed? Identify the number of different type of medications the person is taking per day. 3. (This includes prescribed and unprescribed medication) If the person takes four or more different type of medications, place a tick in the YES column. Please circle if any recent change in medication and please circle if there has not been a medication review. Please insert which chemist/address that dispenses their medication in comments box. 4. How assessed? Ask the person/carer if they have been diagnosed with a stroke or Parkinson s disease? If yes, place a tick in the YES column. 5. How assessed? Ask the person/carer if they feel unsteady when standing and/or whilst walking? If yes, place a tick in the YES column. Another way to find out if they have problems with their balance is to ask the person a question while the person is walking. Keep walking while you do so. If the person stops walking immediately or as soon as they start to answer they are at higher risk of falling and place a tick in the YES column. If there is a sway (i.e the person raises their arms or takes another step to maintain balance) in standing, place a tick in the YES column 6. How assessed? Ask the person to stand up from a standard height chair (ie. The seat is at knee height) without using their arms to assist to stand up? If they are unable to stand up without using their arms to assist, place a tick in the YES column. 7. Consent: Mental Capacity: A person must be assumed to have capacity unless it is established that he/she lacks capacity A person is not to be treated as unable to make a decision unless all practical steps to help them to do so have been taken without success A person is not to be treated as unable to make a decision merely because they make an unwise decision Anything done for or on behalf of a person who lacks mental capacity must be done in their best interests Anything done for, or on behalf of, people without capacity should be the least restrictive of their basic rights and freedoms 8. Use of Comments Box: Please indicate whether the form was completed with the help of a carer. Complete carer s details as appropriate. Also use for additional information that will be helpful/useful for future management. If patient has a history of dementia/neurological problems/palliative care needs. Name & Address of chemist where their medication is dispensed. NB Standard Falls and Health and Wellbeing Information to be given by the assessor to all who have a level 1 screening undertaken. The following leaflet should be obtained (free of charge) from Age UK head office www.ageuk.org.uk/healthandwellbeing Tel: 0800 169 65 65 Staying Steady: Improving Your Strength and Balance(AgeUKIG14) AGREED ACTION PLAN AND REFERRAL PROCESS: Score 2 yes responses:- If the person has fallen and is on four or more medications, has HAD a recent change in medication and has NOT had a recent medication review - the falls prevention coordinator will refer to the community pharmacist. If the person has fallen and there is a problem with the persons strength or balance the falls prevention coordinator will Send information re local exercise activities. If there is a history of blackouts or unexplained falls, the falls prevention coordinator will inform the GP and the need for onward referral to a Level 3 specialist falls clinic will be considered. Score 3 or more yes responses: The Falls Prevention Coordinator will refer the person for a level 2 multi-factorial falls assessment. Fallslevelonecasefindingtoolrevised April 2011