Bone Metabolism PDF

Bone metabolism CTM Chra Sidik (adapted slides from the original presentation by Marianne Rial) Learning outcomes By the end of the session, you be able to : Understand the processes behind bone re- modelling Define what osteoporosis is Explain the common factors that put a patient at...

Bone metabolism CTM Chra Sidik (adapted slides from the original presentation by Marianne Rial) Learning outcomes By the end of the session, you be able to : Understand the processes behind bone re- modelling Define what osteoporosis is Explain the common factors that put a patient at risk of osteoporosis Compare and contrast three treatment options available for treating osteoporosis and explain how they work Why are our bones important? ❑Connective tissue What are the bones 3 main functions? ❑Mechanical i.e. Movement ❑Metabolic ❑Protection Bone Remodelling/Metabolism  What happens to our bones with age? During 25 years to 35 childhood and After 35 years years adolescence Age and bone mass  Nutrition Lifestyle factors Genetics Hormones Physical Activity Age Regulation of bone metabolism Osteoporosis What exactly is this ? A disease characterised by low bone mass, a deterioration of bone tissue, leading to enhanced bone fragility and an increase in fracture risk Diagnosis DEXA scan – looks at bone density Risk factors and causes of osteoporosis Female sex Thyroid imbalance Increasing age Smoking, alcohol, lack of exercise Family history Some drugs- eg corticosteroids, PPIs Caucasian or Asian Low calcium intake Low BMI Low oestrogen levels  DEXA scan This is an X-ray that measures DEXA stands for "dual energy X- It is quick and doesn't hurt! bone mineral density (BMD). ray absorptiometry". Dexa scan What is the difference when compared to healthy bones?  Overview: Think about reasons why a patient may be high risk ways of You can use an online tool NICE recommends FRAX or Qfracture assessing a http://www.qfracture.org/ patient https://www.sheffield.ac.uk/FRAX/tool.aspx?country=1 Remember to think about vitamin D deficiency and poor calcium intake Remember to consider risk of falls  Prevention of fractures 1st line treatments : bisphosphonates Examples of oral treatments are: Alendronate, risedronate, These affect osteoclasts Think about why this will help? Bisphosphonates Mode of action  ▪ Inhibit osteoclasts so therefore bone resorption ▪ Attach to binding sites on bony surfaces that are undergoing active resorption Mode of ▪ Impairs osteoclasts ability to bind to surface (nitrogen-containing bisphosphonates) action ▪ Promote osteoclast apoptosis (non-nitrogen containing bisphosphonates) ▪ Also beneficial effect on osteoblast Counselling Points for Bisphosphonates – 4 POINTS Should be taken on an empty stomach, at least 30 minutes Swallow whole before breakfast and other medications Stand or sit upright Take with plenty of for 30 minutes after water whilst administration (do standing or sitting not lie down upright immediately) Use your BNF!!  Why are these counselling points important? Joints Are Flexible Jaw osteonecrosis Risk is higher with IV bisphosphonates than oral Highest risk with zolendronate Patients who have a poor dental status and cancer should have a dental check-up before starting bisphosphonate treatment(or as soon as possible after starting treatment) Counselling points to patients: maintain good oral hygiene, have routine dental check-ups, report oral symptoms; pain, swelling, non-healing sores or discharge during treatment Auditory osteonecrosis (external auditory canal) Rare but has been reported mainly in patients receiving long term therapy (2 years+) Counselling points to patients: discharge, ear pain, ear infection whilst on bisphosphonate Femoral fractures (atypical) Rare but has been reported in patients receiving long term therapy Counselling points to patients: any thigh, hip or groin pain during treatment with a bisphosphonate If deemed inappropriate, benefits vs risks = discontinue Osteonecrosis Denosumab ▪ An injection given every 6 months ▪ A monoclonal antibody – ‘MAB’ ▪ RANKL inhibitor ▪ Receptor activator of nuclear factor kappaB Denosumab Raloxifene ▪ SERM….which means ▪ Selective oestrogen receptor modulators ▪ It stimulates osteoblasts ▪ It also inhibits osteoclasts ▪ Consider side effects ▪ Hot flushes, leg cramps ▪ Increased risk DVT (uncommon), small increase in stroke Teriparatide ▪ A recombinant parathyroid hormone ▪ Should be initiated by a specialist ▪ Used for both men and women ▪ Given as a subcutaneous injection on a daily basis ▪ Can only be used for up to 24 months ▪ Calcium levels need to be monitored carefully  Why will this help? Hormone What are the other replacement therapy considerations? Potential side effects?  Help you to relate the theory in the lectures to a 'real-life' case study Osteoporosis Ensure you understand the disease the patient is suffering from case study How the pharmacology of the drugs helps to treat this disease The case that we are going to consider… Mrs Ivy Field (aged 78) fell on the stairs in her home and has severe wrist pain with swelling and displacement. It was confirmed that it was a fracture and has been set in a cast and given analgesia. Social history: Ex-smoker. Has occasional alcohol. She is fully mobile but does not tend to exercise. She lives with her husband who has no current significant health issues. Family History: Her mother died of a stroke and suffered from osteoporosis. Her father died from an MI. Previous medical history: Occasional insomnia. Pain in hip and knees, takes paracetamol once or twice a day. Mrs Field’s Drug history Aspirin 75mg daily Zopiclone 3.75mg at night prn Paracetamol 1g QDS prn Question 1 What test is likely to be carried out and why? DEXA scan This is an X-ray that measures bone mineral density (BMD). DEXA stands for "dual energy X-ray absorptiometry". DEXA scans are often used to diagnose osteoporosis It is quick and doesn't hurt! DEXA scan results T scores between +1 and - 1 show normal bone mineral density. Scores between -1 and -2.5 indicate Osteopenia Less than -2.5 indicate Osteoporosis A result of -3.0 shows severe osteoporosis. Question 2 What risk factors does this patient have for osteoporosis? All Risk factors and causes of osteoporosis Female sex Thyroid imbalance Increasing age Smoking, alcohol, lack of exercise Family history Some drugs- eg corticosteroids, PPIs Caucasian or Asian Low calcium intake Low BMI Low oestrogen levels Question 3 What other diagnostic tools could be used in osteoporosis? Question 4 Consider the following three treatment options; explain their mode of action and common side effects? -Premarin -Alendronate -Raloxifene Consider the pros and cons for each options. Which one would you choose? Premarin A hormone replacement therapy Contains oestrogens (and progesterones) Oestrogens – stimulates osteoblast function Risks associated with HRT Increased chance of breast, endometrial, ovarian cancer Stroke and DVT Raloxifene SERM Selective oestrogen receptor modulator Stimulates oestrogen receptors in the bone Bisphosphonates Bisphosphonates- mode of action What happens next… Ivy is prescribed alendronate 10mg once daily and adcal D3 one twice daily Question 5 a)What are the aims of treatment in this patient? b)Explain the main counselling points regarding her new medication. Counselling Points for Bisphosphonates – 4 POINTS Swallow whole Should be taken on an empty stomach, at least 30 minutes before breakfast and other medications Take with plenty of water whilst standing or sitting upright Stand or sit upright for 30 minutes after administration (do not lie down immediately) Why are these counselling points important? Joints Are Flexible Jaw osteonecrosis Risk is higher with IV bisphosphonates than oral Highest risk with zolendronate Patients who have a poor dental status and cancer should have a dental check-up before starting bisphosphonate treatment(or as soon as possible after starting treatment) Counselling points to patients: maintain good oral hygiene, have routine dental check-ups, report oral symptoms; pain, swelling, non-healing sores or discharge during treatment Auditory osteonecrosis (external auditory canal) Rare but has been reported mainly in patients receiving long term therapy (2 years+) Counselling points to patients: discharge, ear pain, ear infection whilst on bisphosphonate Femoral fractures (atypical) Rare but has been reported in patients receiving long term therapy Counselling points to patients: any thigh, hip or groin pain during treatment with a bisphosphonate If deemed inappropriate, benefits vs risks = discontinue Question 7 The junior doctor on your ward wants to know a little more about the treatments available for osteoporosis. He would like to know how denosumab works. Can you explain it? Is there any additional therapy a patient should receive if they are taking this drug? Denosumab References NICE pathway for osteoporosis: https://pathways.nice.org.uk/pathways/osteoporosis The SIGN guidelines for osteoporosis: https://www.sign.ac.uk/media/1812/sign-142-osteoporosis-v3.pdf https://www.nhs.uk/conditions/dexa-scan/what-happens/ https://www.youtube.com/watch?v=LCfV_u0FuOs https://www.ncbi.nlm.nih.gov/books/NBK470248/ https://www.youtube.com/watch?v=ZTBH61OQZTU Learning outcomes By the end of the session, you be able to : Explain what the term bone re-modelling means Define what osteoporosis is Explain the common factors that put a patient at risk of osteoporosis Compare and contrast three treatment options available for treating osteoporosis and explain how they work