MPharm Programme. Osteoporosis in Practice (L4) Louise Statham- Senior Lecturer in Clinical Pharmacy

MPharm Programme Osteoporosis in Practice (L4) Louise Statham- Senior Lecturer in Clinical Pharmacy Louise.statham@sunderland.ac.uk Slide 1 of 47 MPHM13 Module Introduction

Aims This lecture will build on the osteoporosis lecture you received at level 3, focusing on practical issues that are relevant both to practice and also potentially for your OSCE stations/exams. Medication history taking of a complex regimen, Critical appraisal of a prescribed medication regimen and appropriateness for the patient, POM Counselling - how to take the medication Slide 2 of 47 MPHM13 Module Introduction

Relevant Learning Outcomes 3 Assess and critically appraise a patient medication and case history and identify possible problems associated with medicines management and the effect of other diseases or conditions on the choice of medicines. 4 Objectively analyse the rationale underlying the treatment of common diseases, including the use of pharmacological therapy, non-pharmacological therapy and complementary medicine with consideration of the evidence base underpinning Slide 3 of 47 MPHM13 Module Introduction

Osteoporosis: Increased # Risk A progressive systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue with a consequential increase in bone fragility and susceptibility to fracture - WHO-94 Refer to L3 Lectures for pharmacology, incidence and basic pharmacy practice Slide 4 of 47 MPHM13 Module Introduction

Recap Quiz: Osteoporosis is.(t/f) a) Asymptomatic, but increases the risk of fracture b) Osteoporosis is diagnosed by DXA scan, where T- score is less than -1 c) Risk factors include previous fracture, excess alcohol intake, rheumatoid arthritis and parent history of hip fracture d) Pharmacists can use FRAX tool with or without DXA to assess someone s risk of fracture e) Hip fracture is potentially the most serious consequence of osteoporosis f) Treated with bisphosphonates as first line agents Slide 5 of 47 MPHM13 Module Introduction

Case Study Mrs Cole (68 years old) presents with severe back pain- no major trauma. X-ray shows vertebral fractures at L3 and L4 PMH: Previous wrist fracture 2 years ago, Hypertension, COPD, smoker, early menopause (had HRT initially but did not tolerate) What are Mrs Cole s risk factors for fracture?? Slide 6 of 47 MPHM13 Module Introduction

Case Study: Risk factors? Fragility Fracture increases # risk especially multiple/ recent. Vertebral fracture was atraumatic COPD secondary cause: often SMOKERS, repeated STEROID courses, often low body weight 68 yrs, female, Previous wrist fracture 2 years ago, Hypertension, COPD, smoker, early menopause (had HRT initially but did not tolerate) Increasing age and female increase risk (though still reasonably young in this context) Slide 7 of 47 MPHM13 Module Introduction Early menopause: sharp decline in BMD after menopause- significant risk factor if go through process early (<45yrs). Note HRT would have offered some protection if tolerated.

Age Falls Alcoh ol XS Sex Parent Hip # Seden -tary Family Hx Osteop orosis Low BMI Increased Fracture Risk Hyperparathyroidism Hypogonad ism Low Vit D IBD Smoking Early meno pause Coeliac Steroids RA Drugs lots Slide 8 of 47 MPHM13 Module Introduction

Case Continued Mrs Cole is on an orthopaedic ward and has been flagged by the Fracture Liaison Team (FLT) for a DXA Scan Bone Density Results: Lumbar Spine: T-3.0 Femoral Neck: T-2.5 Z-1.8 Z-1.0 Total Hip: T-2.6 Z-1.1 What do the test results mean? Slide 9 of 47 MPHM13 Module Introduction

What do the test results mean? Bone Density Results: Lumbar Spine: T-3.0 Z-1.8 Femoral Neck: T-2.5 Z-1.0 Total Hip: T-2.6 Z-1.1 Osteoporosis as T score is -2.5 or less (standard deviations from young healthy norm) Low bone density for age (Z-score compares with healthy person of same age) Slide 10 of 47 MPHM13 Module Introduction

Could Mrs Cole s fracture risk be quantified? Slide 11 of 47 MPHM13 Module Introduction

FRAX or QFracture Note: there are NICE guidelines for fracture risk assessment. You should be familiar with these. www.shef.ac.uk/frax Can add DXA result if known FRAX can be used to determine whether to start tx, offer lifestyle advice or refer for DXA (with common sense). It can also help patient to quantify risk Slide 12 of 47 MPHM13 Module Introduction

What treatment should be offered to Mrs Cole to reduce risk of further fracture? Slide 13 of 47 MPHM13 Module Introduction

Recap: Initiation of treatment Identify high fracture risk patient who would benefit from treatment e.g. using FRAX tool, DXA First line treatment is Alendronic acid Appropriate? Yes. If no contraindications: *INFORMATION TO PATIENT* Shared decision making process. No e.g. renal impairment, hypocalcaemia, GI risk factors +/- Calcium/ Vitamin D Not suitable or not tolerated? Consider whether Risedronate would be appropriate Yes No Slide 14 of 47 MPHM13 Module Introduction Refer to secondary care/ specialist for alternative

Case Continued Mrs Cole is prescribed 70mg Alendronic acid once weekly Should she be prescribed calcium and vitamin D tablets as well? Slide 15 of 47 MPHM13 Module Introduction

Should she be prescribed calcium and vitamin D tablets as well? Most osteoporosis treatments licensed to be used alongside calcium/vitamin D- always consider??increased MI Risk with calcium supplements, evidence inconclusive MHRA Oct 2011 Advice for healthcare professionals: Consider benefits and risks on individual basis. Consider for all postmenopausal women on osteoporosis treatment unless confident that dietary intake adequate and vitamin D replete The National Osteoporosis Society advises that increasing dietary intake in those with low intakes of calcium and vitamin D is considered preferable to supplements. Take into account dietary intake and give supplements if it is necessary. Slide 16 of 47 MPHM13 Module Introduction

Ca & Vit D Supplements: Practical Points If dietary calcium intake poor/ housebound or institutionalised recommend Diet: Need at least a pint of milk per day (700mg) in terms of calcium requirements (can come from other sources eg yoghurt, cheese, green veg etc) If not sure can use a calculator e.g. http://www.cgem.ed.ac.uk/research/rheumatological/calcium-calculator/ Practical points: Calcium less well tolerated than vitamin D component (e.g. nausea, constipation) Lots of different preparations chewable, caplet, soluble, liquid etc Some preparations contain peanut oil/gelatin If calcium in diet OK can just give vitamin D alone (e.g. 800 units) unless replete (Note: DoH recommends we should ALL consider taking vitamin D during Oct- March https://www.gov.uk/government/news/phe-publishes-new-advice-onvitamin-d ) Slide 17 of 47 MPHM13 Module Introduction

Case Continued Mrs Cole s dietary calcium intake has been assessed to be low. She is prescribed Calcichew D3 Forte two tablets daily She is counselled very well on her new medications by a Level 4 Pharmacy student from the University of Sunderland who referred to their L3 notes (:hint) Slide 18 of 47 MPHM13 Module Introduction

Case Continued Mrs Cole has been taking the Alendronic acid and calcium for a few weeks now and you see her in the community pharmacy you are working in: you ask how she is getting on She tells you that she has been taking the Alendronic acid and calcium but she has been getting very troublesome heartburn and she is not sure whether she should continue to take them. What should you do? Slide 19 of 47 MPHM13 Module Introduction

What should you do? First check that she has been taking the Alendronic acid correctly as if not GI sideeffects more likely First thing in morning on empty stomach with full glass of water; wait half an hour before other medicines, breakfasts, cups of tea etc. Don t lie back down for at least 30 min. Note calcium should be taken at least 2-4 hours after or omit on day of Alendronate Slide 20 of 47 MPHM13 Module Introduction

Case Study Continued Mrs Cole has been taking the medication correctly. You advise that she may need to switch treatments. What are her options? Slide 21 of 47 MPHM13 Module Introduction

What are her Options? Alternative oral BP? Risedronate may cause fewer GI side-effects therefore could trial this Strontium? No longer an option- discontinued by manufacturer Parenteral BP? e.g. Zoledronic acid This would be a once yearly infusion she would have to attend hospital for. Blood tests first to check kidney function, calcium, vitamin D Denosumab 6 monthly subcut injection first in hospital then via GP. Blood tests before each injection to check kidney function, calcium & vitamin D Less likely options: Raloxifene (specialist only, causes menopause like symptoms and increased risk of VTE, less evidence than BPs etc,?reduced breast ca risk); HRT (not suitable here); Teriparatide (only if meet NICE criteria and not v effective at hip) Refer to L3 notes for more info on these drugs Slide 22 of 47 MPHM13 Module Introduction

Administration of Selected Drugs Note you will be expected to counsel patients appropriately on these medications- examples in L3 Osteoporosis in Practice lecture Slide 23 of 47 MPHM13 Module Introduction

Clinical Updates: Strontium Strontium has been discontinued by the manufacturer (2017) and is no longer an option to treat osteoporosis Prescribing restrictions due to increased cardiovascular risk meant that the product was no longer commercially viable and the company made a decision to withdraw All patients switched to suitable alternative Slide 24 of 47 MPHM13 Module Introduction

Case Continued Mrs Cole is switched to Risedronate which she tolerates but she has another fracture after 2 years; what should you do? Slide of 47 MPHM13 Module Introduction

Fracture on treatment BPs reduce risk of fracture by approx. 50% therefore there will always be some people who fracture on treatment. Carry out following checks and suspect treatment failure if more than one fracture or deterioration in DXA results etc Check ADHERENCE most common cause of treatment failure Check ADMINISTRATION- inadvertently taking with food/drink/other medications or taking calcium supplements too close to BP can reduce absorption leading to treatment failure Check ADVERSE effects- common reason for patients not taking treatment regularly Slide 26 of 47 MPHM13 Module Introduction

Case Continued Mrs Cole admits that she has not been taking the Risedronate regularly as she started to find it was sticking in her throat Mrs Cole is switched to Zoledronic acid infusions What are the main potential short term and long term side effects that should be discussed with Mrs Cole? Slide 27 of 47 MPHM13 Module Introduction

Side-effects of Zoledronic acid? Short term Flu-like symptoms common Hypocalcaemia Renal impairment Long-term Rare Osteonecrosis of Jaw Atypical Fracture Osteonecrosis of auditory canal Associated Counselling Recommend prophylactic paracetamol Important to have blood tests to check calcium and vitamin D OK before infusion (vitamin D helps calcium absorption) Blood tests to check kidney function is OK before starting Associated Counselling Good dental hygiene, regular dental check ups (any dental work prior if possible); reminder card should be given Report any unexplained hip, thigh or groin pain (X-ray to rule out) Report any ear pain, discharge from the ear, or an ear infection during BP treatment See BNF for MHRA info on side effects Slide 28 of 47 MPHM13 Module Introduction

Mrs Cole s Blood Results are as follows: Creatinine Clearance 60ml/min (you have calculated this after checking serum creatinine levels using cockroft gault equation) Calcium: normal range Vitamin D: 60nmol/L Should be >35ml/min SPC says use CG equation Should be >50nmol/L; if not give loading vitamin D Slide 29 of 47 MPHM13 Module Introduction

Bloods are OK so Zoledronic acid can go ahead. How long should Mrs Cole stay on Zoledronic acid for? Slide 30 of 47 MPHM13 Module Introduction

Bisphosphonate Duration MHRA: Review bisphosphonates, particularly after 5 or more years of use due to increased risk of atypical fracture (NB. Zol 3 yrs) Until recently no national guidance- some info now produced by NOGG https://www.sheffield.ac.uk/nogg/downloads.html Drug holiday = Stop bisphosphonate, usually for 1-3 years Increasingly used in practice with bisphosphonate medications; Long t1/2 some sustained effect on cessation May continue beyond 5 years in very high fracture risk, especially if vertebral fractures In this case advise that treatment will be reviewed after 3 years. At that stage a decision will be made with patient as to whether to continue or pause treatment. (Note for other BPs generally review at 5 years) Slide 31 of 47 MPHM13 Module Introduction

Any questions about the case? Slide 32 of 47 MPHM13 Module Introduction

Drug History taking in osteoporosis Note that IV preparations given in hospital may not show up on a GP list E.g. zoledronic acid, IV ibandronate or sometimes SC denosumab Injections often missed (or occasional errors where people have been on PO + IV) SC Teriparatide is prescribed less commonly but Usually issued by a homecare company (may not be on GP list) Kept in fridge What day of the week/ month? Or when was last injection/due? Slide 33 of 47 MPHM13 Module Introduction

Drug history taking in osteoporosis Check adherence- often poor Check administration technique and timing of calcium/ other meds Patients may be on a drug holiday Ask about recently stopped medications. Have they ever taken a medication for bones? How long have they been taking it? Usually reviewed after 5 yrs (3 yrs for Zol) then consider drug holiday 1-2 yrs or continue 7-10yrs. See NOGG or local guidance. Slide 34 of 47 MPHM13 Module Introduction

Clinical Review What is the fracture risk? Is bone protection indicated? Prescribe/advise Adherence? Has the patient fractured on treatment? Risk reduction ~50% so some fractures inevitable but repeated fractures particularly concerning Adherence? Interactions? Treatment failure? Blood tests: changes to renal function, calcium status? Is medication still appropriate? <35ml/min Alendronate, <30ml/min Risedronate etc Hypocalcaemia must be corrected Slide 35 of 47 MPHM13 Module Introduction

Clinical Review (continued) Consider calcium/vitamin D supplementation Always consider, though may reasonably omit if calcium dietary intake adequate (>700mg) Parenteral treatments Calcium, vitamin D, kidney function should be checked prior to each injection Correct hypocalcemia before injections given Vitamin D loading + maintenance if vitamin D low Drug interactions? - Consider timings of medications Side-effects? Pain control? E.g. vertebral fracture Slide 36 of 47 MPHM13 Module Introduction

Clinical Review (continued) Falls risk/ polypharmacy medication review Duration of treatment?review?drug holiday Contraindications? E.g. patient has developed swallowing difficulties/can t follow administration requirement, Women of childbearing potential etc Adverse drug reactions? Recognition, Treatment review,? Yellow card Invasive dental procedures Consider withholding treatment (ONJ risk), particularly for parenteral antiresorptives Slide 37 of 47 MPHM13 Module Introduction

Patient Counselling At initiation: What is it for/benefits Administration requirements Common side-effects Review/ long-term side effects Questions Patients often want to discuss the risks/benefits of choice of medications Support/counselling also required on an ONGOING basis. Prophylactic treatment requires a lot of motivation! Slide 38 of 47 MPHM13 Module Introduction Examples in L3 Lecture

Interpretation of Blood Tests Glennis (68yrs old) is due her 6-monthly denosumab injection; you are the practice pharmacist and need to follow up her bloods to check they are OK prior to her injection. Bloods: Sodium 141mmol/L (133-146) Potassium 4.9 mmol/l (3.5-5.3) Urea 8.9mmol/L (2.5-7.8) Creatinine 113umol/L (65-105) Adjusted calcium 2.26 mmol/l (2.20-2.60) Phosphate 0.84mmol/L (0.8-1.5) Total vitamin D 63nmol/L (>50 = vit D sufficiency) Slide 39 of 47 MPHM13 Module Introduction

Glennis: Bloods Review 1. Adjusted calcium normal 2. Vitamin D satisfactory 3. Renal function normal -> calculate renal function- egfr 44ml/min/1.73m 2 BNF: Renal impairment increased risk of hypocalcaemia if egfr less than 30 ml/minute/1.73 m 2 monitor plasma-calcium concentration; see also Cautions; atypical femoral fractures (see MHRA/CHM advice); osteonecrosis of the jaw consider temporary interruption of treatment if occurs (see MHRA/CHM advice); hypocalcaemia (see MHRA/CHM advice) Slide 40 of 47 MPHM13 Module Introduction

Glennis: Plan Renal function is impaired, but above the threshold suggested by BNF Worth considering whether this is acute or chronic kidney impairment Risk with Denosumab is hypocalcaemia Calcium in range Vitamin D in range Renal function at a satisfactory level Plan: Proceed with injection Slide 41 of 47 MPHM13 Module Introduction

Mini Cases: Joan Joan is a 68 year old lady She is sick of being on all of these tablets. She lives at home and is relatively mobile For osteoporosis she takes Alendronic acid 70mg once weekly and calcium/vitamin D one tablet twice daily. How could you manage this situation? Slide 42 of 47 MPHM13 Module Introduction

Mini Cases: Margaret Margaret is 79 and attends for her routine annual review. She has been taking Alendronic acid for 2 years. She is well in herself. She has stage 3b CKD which has been stable over the last few years at 36-37ml/min/1.72m 2. Her latest reading is 35ml/min/1.72m 2 Discuss any concerns you may have. What would you do in the case of AKI? Slide 43 of 47 MPHM13 Module Introduction

Mini Cases: Mary It has been decided that your patient Mary needs to start bone protection medication as she is at increased fracture risk. You discuss the usual first line treatment but she tells you that she is not keen. Her friend Mrs Jones was on these tablets and had horrific side-effects. How would you manage this situation? Slide 44 of 47 MPHM13 Module Introduction

Mini Cases: Mavis Mavis is an anxious character and is worried about everything. She fell and broke her wrist last month and has been put on some once weekly medication to strengthen her bones. However, she hasn t got into the swing of taking it yet and missed her dose this week. How would she handle a missed dose? What measures might help her to get into a routine with her medication? Slide 45 of 47 MPHM13 Module Introduction

PHARMACIST Interventions to Reduce Fracture Risk Identification of risk factors for fracture and assessment of overall fracture risk Refer/interpret DXA scan Identification of secondary causes Lifestyle advice Medication (prescribing, advising) Shared Decision Making Advice to patients and prescribers Identification and advice re side-effects Treatment review (bone protection plan, renal function, co-morbidities etc) Multi-disciplinary team (fracture liaison, ortho-geris, GPs, spec nurses, physios, consultant etc) Drug holidays? Medication review- (reduce polypharmacy, reduce falls risk, reduce fracture risk) Administration, timings, adherence review/advice Slide 46 of 47 MPHM13 Module Introduction

Questions? Slide 47 of 47 MPHM13 Module Introduction