Bones 🦴 Flashcards
(69 cards)
Poor bone health is commonly associated with menopause. What risk factors are present that increase the risk of osteoporosis and what considerations should be made about improving bone health and preventing fractures for TY?
Risk factors:
Female sex
Increasing age
Smoking
Alcohol
Previous fracture
Oral corticosteroids
Rheumatoid arthritis
Parental history of hip fracture
BMI over 18.5
Reduce bone mineral density(BMD):
Endocrine disease
Diabetes mellitus, Hyperthyroidism, and hyperparathyroidism
Gastrointestinal conditions that cause malabsorption
Crohn’s disease, Ulcerative colitis, Coeliac disease, and Pancreatitis - chronic.
Chronic kidney disease
Chronic liver disease
Chronic obstructive pulmonary disease
Menopause
Immobility
Body mass index of less than 18.5 kg/m²
Do not reduce BMD:
Increased age
Oral corticosteroids
Smoking
Alcohol
Previous fragility fracture
Rheumatological conditions
Rheumatoid arthritis, other inflammatory arthropathies
Genetic
Parental history of hip fracture
Other:
Selective serotonin reuptake inhibitors
Proton pump inhibitors
Anticonvulsant drugs, in particular enzyme-inducing drugs(carbamazepine)
To improve bone health and prevent fractures:
Bone density testing (DEXA scan)
Hormone replacement therapy(menopause-oestrogen deficiency): e.g. oestrogel
Bisphosphonates (bone-sparing treatment)
Increase level of calcium and vitamin D via diet or supplements
Regular weight bearing exercise to strengthen bones
Keep smoking cessation
Limit alcohol
What are Noreen’s risk factors for a fragility fracture? Calculate her FRAX score and consider how this score can be used to discuss treatment options holistically?
Age and postmenopausal
At 65 and postmenopausal, naturally higher risk of osteoporosis and fragility fractures due to decreased oestrogen, which affects bone density. Decreased bone density .
BMI
18.4 is underweight, which means a higher risk of fractures due to lower bone density.
DEXA Scan T-Scores:
Her T-scores indicate osteoporosis:
Hip T-score: -3.0 (indicates osteoporosis)
Spine T-score: -1.0 (borderline osteopenia/normal)
The hip T-score of -3.0 is particularly concerning for fracture risk.
History of Fragility Fracture:
Already had a hip fracture from a fall, so she has experienced a fragility fracture. This is one of the most significant risks of future fractures.
Postural hypotension? - risk of falls
Sitting BP 110/80 mmHg
Standing BP 90/75 mmHg
BP drops when she stands which increases risk of falls → postural hypotension?
Lives alone (increased risk of falls)
Alcohol (increased risk of falls)
Steroids negatively impact bone health
FRAX SCORE:
10 year possibility (%) of major osteoporotic fracture ( hip, spine, forearm, and shoulder) and another one specifically for hips
———-
Calculating:
Age (40–90 years).
Sex.
Body mass index (BMI).
Clinical Risk Factors:
Previous fracture (after age 50).
Parental history of hip fracture.
Current smoking.
Glucocorticoid use (e.g., prednisone for ≥3 months at ≥5 mg/day).
Rheumatoid arthritis.
Secondary causes of osteoporosis (e.g., diabetes, hyperthyroidism, premature menopause).
Alcohol intake (≥3 units/day).
Bone Mineral Density (BMD) (Optional):
Specifically, femoral neck BMD can be entered to enhance accuracy.
Geographic and Population Data:
Country-specific fracture and mortality data are incorporated to adjust risk predictions.
———-
Lifestyle Factors:
Eat a well-balanced diet containing a variety of foods, including grains, fruits and vegetables, nonfat or low-fat dairy products or other calcium-rich foods, and meat or beans each day.
→ currently eats a dairy-free diet - so suggest dairy-free alternatives that are rich in calcium (chia, sunflower seeds, soy milk, tofu, etc)
Lives alone so can be difficult to keep up with eating well
Choose weight-bearing activities such as brisk walking, jogging, tennis, netball or dance.
Reduce alcohol consumption (6 units/week (not over limit but can increase risk regardless)), already stopped smoking
What further pharmacological and non-pharmacological treatments could be offered to Noreen to reduce her risk of future fractures? Make sure you consider the appropriate patient advice.
Pharmalogical
First line - bisphosphonate: alendronate 10mg daily / 70mg once weekly or Risendronate 5mg OD or 35mg once weekly
Take it at same time each time to remember
Calcium and vit D supplements (already on vit D, increase calcium in diet)
Calcium supplements taste chalky so give advice for how it important it is
Non-pharmacological
Take regular exercise (tailored to person) to improve muscle strength.
Encourage:
Walking, especially outdoors, will increase exposure to sunlight, increasing vitamin D production.
Strength training (such as weight training) of different muscle groups (for example hip, wrist, and spine).
A combination of exercise types, for example balance, flexibility, stretching, endurance, and progressive strengthening exercises.
Cognitive ability
Check continence
Monitor Codeine
Eat a balanced diet. Calcium-rich foods, protein. (Eggs fish lean meats leafy greens almonds)
Drink alcohol within recommended limits, as alcohol is a dose-dependent risk factor for fragility fracture.
Look at tripping hazards in house. Ensure her bungalow is fall-proof by reducing tripping hazards, adding grab bars, and ensuring proper lighting.
Falls assessment
Encourage regular vision and hearing checks
Hydration
Small frequent meals
Get up slowly from standing
Adverse effects
Upper gastrointestinal adverse effects, such as dyspepsia or reflux — these are common in the first month of treatment and often improve with continued use.
Symptoms of atypical fracture, including new onset hip, groin, or thigh pain.
Symptoms of osteonecrosis of the jaw, including jaw pain, swelling, and redness.
Regular Monitoring
Need for follow-ups, including DEXA scans, bloods for calcium and vitamin D levels, and kidney function.
What chemical properties of bisphosphonates potentially contribute towards their extremely poor oral bioavailability? What formulations are available and what are their respective advantages for both administration and delivery, and the patient
extremely poor oral bioavailability, generally less than 1%, very little of drug taken orally actually reaches systemic circulation.
Absorption Challenges:
Highly Polar and Hydrophilic:
Bisphosphonates have two phosphonate groups, making them poorly absorbed through lipid-rich GI membranes. They are really big and polar (negative change) and highly hydrophilic which is the opposite needed for good absorption.
Charge and pKa:
Strongly negatively charged at physiological pH, limiting passive diffusion across cell membranes.
Affinity for Divalent Cations:
Bind to calcium, magnesium, and iron in food, forming insoluble complexes that reduce absorption.
Patients are advised to take bisphosphonates on an empty stomach and avoid supplements or certain foods during administration.
Poor Permeability:
High molecular weight and hydrophilicity prevent effective passive or active transport across the GI tract.
Available Formulations and Their Advantages:
Oral Tablets (Standard Formulations):
Examples: Alendronate, Risedronate, Ibandronate.
Advantages: Non-invasive, convenient, and traditional.
Challenges:
Low bioavailability despite taking on an empty stomach.
Requires remaining upright for 30–60 minutes to minimize GI irritation.
Common GI side effects.
Delayed-Release Oral Formulations:
Example: Delayed-release Risedronate.
Advantages:
Reduces GI irritation by releasing the drug in distal GI sections.
Can be taken with food, improving patient adherence.
Challenges: Bioavailability is still limited by the drug’s chemical properties.
Intravenous (IV) Formulations:
Examples: Zoledronate, Ibandronate, Pamidronate.
Advantages:
100% bioavailability by bypassing the GI tract.
Eliminates absorption issues and GI side effects.
Less frequent dosing (e.g., annually for zoledronate), improving adherence.
Challenges:
Invasive and requires healthcare facilities.
Higher costs and reduced patient convenience.
Bisphosphonates instructions
Empty stomach. 30 -60 minutes before food / other meds
Swallow whole with water
30mins sit / stand up right to prevent irritation
Eat calcium and vitamin D and iron and protein rich foods
Side effects
Upper gi effects: swallowing difficulty, nause, discomfort, oesophageal ulcers
Atypical fractures
Osteonicrosis of jaw
The patient returns in 12 months for their annual medication review. On reviewing their recent blood results, you note their renal function has deteriorated such that creatinine clearance is 34 mL/min. You also note a recent acute issue for her codeine and paracetamol. What adjustments need to be made to her treatment?
Codeine: reduce the dose or replace by low dose oxycodone or hydromorphone
Codeine is metabolised in the liver while the active metabolites are excreted by the kidney. The accumulation of their metabolites may cause neurotoxic symptoms.
Oxycodone and hydromorphone are safe in renal impairment patients but need dose adjustment and monitoring.
Bisphosphate: replace by Denosumab
Bisphosphate is excreted by the kidney and has potential nephrotoxicity. BNF recommends: avoid if creatinine clearance less than 35 ml/minute.
Denosumab is not metabolised or excreted by the kidneys, and does not accumulate in kidneys. Denosumab is given by s.c. injection twice per year. So denosumab is more suitable for patients with severe renal impairment.
Monitor: hypokalemia
Paracetamol: adjust dosing interval
Paracetamol is generally safe in renal impairment. But we can extend the dosing interval to 6-8 hours in severe renal impairment.
Adcal D3: continue with caution
Periodic check plasma calcium levels and urinary calcium excretion.
Calcium and vitamin D3 is beneficial for the patient of osteoporosis
But reduced renal function increased the risk of hypercalcaemia.
Discuss the appropriateness of prescribing trimethoprim to manage HA’s UTI.
BNF Recommendation:
Catheter-associated UTI Treatment:
Trimethoprim: 200 mg twice daily for 7 days.
Extend to 14 days if upper urinary-tract symptoms are present.
Drug Interactions:
Trimethoprim + Ramipril:
Increased risk of nephrotoxicity.
Increased risk of hyperkalaemia, especially with ACE inhibitors, angiotensin-II receptor antagonists, spironolactone, or eplerenone.
Trimethoprim + Methotrexate:
Additive inhibition of dihydrofolate reductase increases the risk of haematological side effects, including methotrexate toxicity.
Possible myelotoxicity and pancytopenia (fatal in some cases).
Manufacturer advises avoiding this combination.
Increased risk of nephrotoxicity.
Alternative Antibiotic:
Nitrofurantoin:
Recommended dose:
100 mg modified-release twice daily.
If unavailable: 50 mg four times daily for 7 days.
Use only if eGFR is above 45.
Not recommended for men with prostate involvement (unlikely to reach therapeutic levels in the prostate).
Common male UTI: Prostatitis (inflammation of the prostate gland).
Patient-Specific Considerations:
Elevated Liver Enzymes:
Liver function tests show significantly elevated ALT, AST, and ALP levels (indicating liver inflammation or damage).
Trimethoprim can stress the liver further and worsen the condition.
Monitoring Requirements:
If trimethoprim is prescribed:
Close monitoring of blood counts and liver function.
Regular follow-ups to assess response and adjust treatment if necessary.
200mg twice daily
7 days
Interaction with methotrexate so withhold MTX
Switch this antibiotic with nitrofurantoin as patient has and normally high lLFTs and is immunosupressed. Still with hold methotrexate even though no interaction.
Don’t need folic acid as stopped trimethoprim and MTX (no antifolic action)
7 days with new
Steroid card
Nitrofurantoin: Take w/ food. Can cause nausea and sickness, can turn urine bright yellow. Avoid live-attenuated vaccines as it can cause the disease to develop e.g. chicken pox as efficacy of vaccine can be affected
Modified release
100mg twice daily
Renal function every two weeks until stable then every 3 months (since already on ramipril too)
Monitor liver function (methotrexate) (LFTs )
Lipid profile
Full blood count
Monitor symptoms of UTI
look for symptomatic improvement
culture sensitivites if no improvements
If changing methotrexate, use steroids to have anti inflammatory effect while new drugs kick in to minimise risk of flare up (bridging)
What safety precautions should prescribers and dispensers follow when supplying methotrexate for an autoimmune condition?
Ensure patient not on trimethoprim (toxcity)
Temporary suspension if unwell / systemic infection
Weekly Dosing of Methotrexate: Key (once weekly) Recommendations, folic acid
Dose & Frequency
Methotrexate should be administered once weekly for autoimmune conditions.
Ensure that both patients and caregivers fully understand the weekly dosing schedule to prevent errors.
Prescription Guidelines
Prescribe only one strength of methotrexate (e.g., 2.5 mg) to reduce the risk of dosage mistakes.
Provide clear, detailed instructions on prescriptions and labels, specifying both the dose and frequency.
Patient Education
Educate patients on potential risks such as blood disorders, liver toxicity, and respiratory issues.
Key symptoms to watch for include:
Sore throat
Easy bruising or bleeding
Nausea
Dark urine
Shortness of breath
Stress the life-threatening risk associated with dosing more frequently than prescribed.
Actions for Healthcare Professionals
Document the specific dosing day in the patient’s medical record to ensure consistency.
Review the patient’s complete medication list to account for polypharmacy and potential interactions.
SAFETY
Photosensitivity Reactions
Methotrexate may cause photosensitivity, including phototoxicity.
Severe reactions can result in secondary infections and other serious complications.
Preventive Measures
Avoid UV light exposure, including:
Intense sunlight
Sunlamps
Sunbeds
Use a high-SPF sunscreen and wear protective clothing when exposed to the sun.
Advise patients to seek medical advice if they experience:
Skin rashes with papules or blistering
Swelling or other severe skin reactions
MHRA Recommendations
Remind patients of the risks associated with photosensitivity.
Emphasize the importance of safe dosing practices, including:
Carrying a patient alert card to ensure adherence to weekly dosing.
Pre-screening Before Initiating Biologics
Screen for Infections:
Latent tuberculosis (TB).
Hepatitis B (HBV) infection.
Hepatitis C (HCV) infection (suggested but not mandatory).
Additional Testing:
Severe diarrhea with fever/bleeding → Check for Clostridium difficile or cytomegalovirus infections.
Liver and kidney function tests.
Full Blood Count (FBC).
Why Pre-screening is Necessary
Prevent reactivation of infections (e.g., TB reactivation can worsen with immunosuppressants).
Baseline tests help monitor potential treatment side effects and early complications.
Educate the patient on the risk-benefit profile of biologics.
Specific Tests for biologics
Liver Function Tests (LFTs):
Detect immune-mediated hepatitis (e.g., from immune checkpoint inhibitors).
Monitor for liver enzyme elevations; adjust or pause treatment if necessary.
Lipid Profile:
TNF inhibitors (e.g., adalimumab, infliximab) → Increased cholesterol and LDL.
IL-6 inhibitors (e.g., tocilizumab) → Elevated cholesterol and triglycerides.
Baseline lipids help assess cardiovascular risk, which is higher in autoimmune patients.
FBC:
Detect neutropenia, thrombocytopenia, or anemia.
Monitor changes in blood cell counts to identify risks like infection or bleeding.
Pregnancy test
Myelinating disease
Anti-tumour necrosis factor (TNF) agents like adalimumab are safe and effective for rheumatologic disorders, but they have been reported to cause demyelinating diseases like multiple sclerosis.
Symptoms of myelinating disease to monitor:
Vision changes.
Tingling or numbness.
Fatigue.
Bladder or bowel problems.
Trouble walking.
Stiff or weak muscles.
Check history if had disease if they have then shouldn’t be on anti tnf therapy
Rheumatoid arthritis is often treated with a biologic or tsDMARD. These treatments are considered to slow down or stop disease progression.
What are the consequences for the patient in terms of how RA affects their health in the short and long term?
SHORT TERM
RA causes joint pain, swelling, stiffness, and fatigue, leading to significant impairment in daily activities and quality of life.
Uncontrolled inflammation can result in systemic symptoms such as fever, malaise, and anaemia.
Begin to feel tired, lose weight and develop nodes under their skin, the pain can make it difficult for some patients to do everyday tasks like go to work to even leave the house.
Increased risk of developing bacterial or viral infections because the pathology of this disease involves the immune system attacking the individual’s own joints and tissues, making it unable to fight real invaders correctly.
increased risk of infection means more likely to miss work, stay home, and thus lose money.
Depression / anxiety
LONG TERM
Persistent inflammation leads to irreversible joint damage as fibrous tissue can form around the joints, and bones can become fused together, causing deformities, and long-term disability. This can attack the wrists, elbows, ankles, knees, hips, shoulders and ribcage.
Increased risk of osteoporosis , infections
Untreated or poorly managed RA increases risk of systemic complications such as cardiovascular disease, kidney and lung complications.
These include scar tissue formation on the lungs as a result of the long-term inflammation of rheumatoid nodules in the lung, which can rupture and lead to the collapse of the lung. It can also lead to pleuritis which is a build-up of fluid in the chest cavity around the lung. Inflammation of tissue surrounding the lungs.
Chronic symptoms and disability can contribute to psychological issues such as depression and anxiety.
Allowing the disease to remain active can result in poorer outcomes, including reduced life expectancy.
What are the direct and indirect costs associated with RA? How does using a biologic or tsDMARD affect those costs and outcomes?
DIRECT
medication (specify)
Medical costs include hospitalisations, imaging, laboratory tests, and medications, particularly biologics and tsDMARDs, which can be expensive- this would mainly be an issue in private health care. Advanced cases may require joint replacement or other surgeries.
Ongoing care costs such as physical therapy and assistive devices.
INDIRECT
Lost productivity due to patients being bedridden and unable to perform daily tasks due to the pain and this would be far greater if it is left untreated
The intangible costs, Psychological and social costs linked to reduced independence and quality of life.
IMPACT of Biologic or tsDMARD
Direct- While biologics and tsDMARDs are costly, their use reduces the need for hospitalisations, surgeries, and other medications such as steroids.
Indirect Costs- Patients with controlled RA are more likely to remain employed, reducing lost productivity. Less disability also decreases reliance on caregivers.
Biologics and tsDMARDs involve high initial costs but they can lead to improved outcomes and potential cost savings over time.
Disease-modifying antirheumatic drug
The two main NICE guidance documents in RA (TA375 and TA715) use DAS28 (Disease Activity Score) and the EULAR response criteria to decide whether to treat someone with biologic or tsDMARDs.
What is DAS28?
The DAS28 measures disease activity in rheumatoid arthritis (RA). DAS stands for ‘disease activity score’, and the number 28 refers to the 28 joints that are examined in this assessment.This involves patient assessments, and inflammation markers, (CRP/ESR). Upon examination a score greater than 5.1 indicates active disease and less than 3.2 indicates well-controlled disease
What are the limitations of this measure?
(DAS28)
Relies on subjective input and may overestimate remission.
Scores may overestimate disease activity due to factors like gender, neuropathy, comorbidities, fixed joint damage, and psychological or physical distress, leading to discrepancies between the score and actual inflammation levels.
Only focuses on 28 joints which excludes joints in the ankles and other parts of the body.
What are the EULAR response criteria?
EULAR Response Criteria (European League Against Rheumatism)
Purpose:
Evaluate treatment response in rheumatoid arthritis (RA) based on changes in DAS28 scores and current disease activity levels.
Criteria:
Good Response:
DAS28 decreases by >1.2 AND
Final DAS28 drops and is ≤3.2 (low disease activity).
Moderate Response:
DAS28 decreases by >1.2, but final DAS28 is >3.2 OR
DAS28 decreases by 0.6–1.2, with final DAS28 ≤5.1.
No Response:
DAS28 decrease is <0.6 OR
DAS28 decrease is 0.6–1.2, but final DAS28 is >5.1 (high disease activity).
Key Points:
Combines absolute change in DAS28 with current disease state.
Helps determine effectiveness of therapies in clinical trials or routine practice.
Tailors treatment adjustments for better disease management.
DAS28
DAS28 (Disease Activity Score in 28 Joints)
What it Measures:
Assesses disease activity in 28 joints for rheumatoid arthritis (RA).
Components:
Tender joint count (TJC28).
Swollen joint count (SJC28).
Patient’s global health assessment (VAS score).
Inflammatory marker (CRP or ESR).
How it Works:
Provides a score ranging from 0 to 10:
<2.6: Remission.
2.6–3.2: Low disease activity.
3.2–5.1: Moderate disease activity.
>5.1: High disease activity.
Limitations:
Excludes Important Joints:
Does not include feet and ankles, which are often affected in RA.
Subjectivity:
Patient-reported outcomes (e.g., VAS) can be influenced by non-disease-related factors like mood or pain perception.
Inflammatory Markers:
CRP or ESR may not always correlate with clinical disease activity.
Non-Specific Swelling:
May not differentiate between active RA and other causes of joint swelling (e.g., osteoarthritis).
Limited Sensitivity:
May not capture subclinical inflammation or disease progression.
These limitations underscore the need for comprehensive assessments alongside DAS28 scores.
What are the differences between (TA375 and TA715)
TA375 is for severe disease, DAS28>5.1, TA715 is for moderate disease (DAS 3.2-5.1). According to the the NICE technology appraisal, it should only be used if severe and DAS28>5.1 and the if the disease has not responded to intensive therapy with a combination of conventional DMARDS.
TA375 recommends biological DMARDs for severe disease but not moderate, due to lack of cost-effectiveness
https://www.nice.org.uk/guidance/ta715/documents/1 -TA375
Adalimumab, etanercept, and infliximab with methotrexate are recommended for active rheumatoid arthritis in adults if:
The disease is moderate (DAS28 3.2–5.1) and not well-controlled with 2+ conventional DMARDs, and
The companies offer these biologics at or below the prices agreed with the Commercial Medicines Unit.
https://www.nice.org.uk/guidance/ta715/evidence/final-appraisal-document-committee-papers-pdf-9194320333 TA715
NICE Technology Appraisals TA375 and TA715 provide guidance on the use of biological therapies for treating rheumatoid arthritis (RA) in adults, focusing on different disease severity levels and specific medications.
TA375:
Scope: Addresses the use of adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab, and abatacept for adults with severe RA (Disease Activity Score [DAS28] >5.1) after inadequate response to conventional DMARDs.
Recommendations:
These biologics, combined with methotrexate, are recommended if:
The disease is severe (DAS28 >5.1).
There is an inadequate response to at least two conventional DMARDs.
Monotherapy with adalimumab, etanercept, certolizumab pegol, or tocilizumab is an option when methotrexate is contraindicated or not tolerated.
Treatment continuation is advised only if there is a moderate EULAR response at six months.
Initiate treatment with the least expensive drug, considering administration costs, dosage, and price per dose.
TA715:
Scope: Focuses on adalimumab, etanercept, infliximab, and abatacept for adults with moderate RA (DAS28 between 3.2 and 5.1) after failure of conventional DMARDs.
Recommendations:
Adalimumab, etanercept, and infliximab, in combination with methotrexate, are recommended if:
The disease is moderate (DAS28 3.2 to 5.1).
There is an inadequate response to at least two conventional DMARDs.
Monotherapy with adalimumab and etanercept is permitted when methotrexate is contraindicated or not tolerated.
Abatacept with methotrexate is not recommended for moderate RA.
Treatment should continue only if there is a moderate EULAR response at six months.
Start treatment with the least expensive drug, considering administration costs, dosage, and price per dose.
Key Differences:
Disease Severity:
TA375 pertains to severe RA (DAS28 >5.1).
TA715 addresses moderate RA (DAS28 3.2 to 5.1).
Medications Covered:
TA375 includes a broader range of biologics: adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab, and abatacept.
TA715 focuses specifically on adalimumab, etanercept, infliximab, and abatacept.
Recommendations for Abatacept:
TA375: Recommends abatacept with methotrexate for severe RA.
TA715: Does not recommend abatacept with methotrexate for moderate RA.
What are osteoblasts?
Derived from mensechymak stem cells
build new bone (b for build)
When they become entrapped into the new bone, the5 nature into osteocytes
What are osteoclasts?
Derived from monocytes
Break down old bone (resorption)
What is osteoporosis caused by?
Reduced osteoblast activity
Increased osteoclast activity
Low peak bone mass
Factors influencing bone turnover
Hormones (oestrogen, testosterone, parathyroid)
Calcium & vitamin D
Weight bearing exercise
Smoking
Alcohol
Medicines: corticosteroids!!!, heparin, warfarin
Bone turnover: sex hormones
Oestrogen: protective effect (action on both osteoblasts and osteoclasts). Low levels = increased rate of bone remodelling = resorption greater than formation. Levels describes ad women become post menopause so risk increases.
Testosterone: protective effect (action on osteoblasts)
Men with low levels = greater risk of osteoporosis
