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Treatment of Major Rheumatic Diseases. Dr Tanya Potter Consultant Rheumatologist. Aims. 1 To pass your exam 2 Encourage safe prescribing (and you will remember that have an exam in this also). Rheumatoid arthritis (RA) or osteoarthritis (OA) most common types seen in clinics (& exams)

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treatment of major rheumatic diseases

Treatment of Major Rheumatic Diseases

Dr Tanya Potter

Consultant Rheumatologist

  • 1 To pass your exam
  • 2 Encourage safe prescribing (and you will remember that have an exam in this also)
Rheumatoid arthritis (RA) or osteoarthritis (OA) most common types seen in clinics (& exams)
  • Dramatically improved treatments in past 20 yrs
  • most common
  • 75% people > 70 radiographic OA F: M 2.5:1
  • Joint space narrowing
  • Osteophytes
  • Subchondral sclerosis
  • Bone cysts
  • Pain relief is key
  • Seek improvement in joint mobility or walking time
    • e.g. how long it takes for pt to walk to end of corridor
  • Quality of life- can use functional measures to see how well person is doing. Use several simple questions:
    • How well can one button clothes?
    • Can make own meals everyday?
    • Gives good reliable data
oa goals of treatment
OA - Goals of Treatment
  • No cure
    • Meds can improve function by reducing pain
  • Can limit final impairment
  • Non-pharmacological and pharmacological


  • Patient education (education leaflets/ websites)
    • Wt loss (10-15 lb weight loss can reduce pain 100%)
    • Every lb gained, X four across weight bearing joint
    • Muscle strengthening important -esp. quads muscle
    • PT & OT important
    • Use devices for joint protection (canes, walkers etc…)
  • Mild to moderate
    • Paracetamol;
    • Topical agents: non steroidals, rubefacients
  • Moderate to severe
    • As above, plus
    • NSAIDs
    • combination analgesics (paracet +opiods) / Opiods/ Tramadol
  • Analgesic/ antipyretic
  • Unknown mechanism of action
  • combo with opiods better response

when can’t use NSAIDs (gu / du/ renal/ warfarin)

  • Doesn’t alter platelet function (bleeding/ surgery)
  • Safer for elderly
  • Caution with chronic liver dz (hepatotoxicity, > 2 gm)
  • Thrombocytopaenia, neutropaenia rare
  • Centrally acting analgesic
    • Use in addition to NSAID
    • Effects mu receptors; Same potency as opiods
    • Can use as adjunctive therapy
    • Less opiod SE; esp constipation/ nausea/ vomiting
      • Balance problems
  • smaller potential of abuse or dose acceleration, (pt needs more drug in shorter time period) c.f. opiods
strong opiods
Strong opiods
  • Use in pt with limited options
    • loss of function due to pain
    • renal or heart disease preventing operation
    • Select pt carefully
  • Use during period of disease flare, then decrease use
  • Limitations
    • Nausea, vomiting, constipation, ***urinary retention
    • Chronic use leads to physical dependence
  • Can use with anti-inflammatory
  • Lots of choice (short or long acting, patches)
  • 25 million NSAID prescriptions/ yr in UK
  • Non selective
    • Aspirin
    • Ibuprofen
    • Naproxen
    • Indomethacin
    • Piroxicam
  • Selective cox 2 inhibiters
    • Celecoxib
    • Etoricoxib
    • Meloxicam
    • etodolac
nsaid risk
NSAID risk
  • How many GI bleed admissions annually in the uk?
  • What percentage are likely to due to NSAIDs?
  • How many deaths annually?

Upper GI complications

  • 65,000 emergency upper GI admissions p.a. in UK
  • 12,000 of these admissions (including 2,230 deaths) attributable to NSAID use
  • Further 330 attributable deaths occur in community
  • ~2% of NSAID users admitted annually for GI emergencies

GI event may be devoid of warning symptoms

Many patients asymptomatic prior to serious NSAID-associated GI event (bleeding, perforation)

n = 141

n = 1,921





without symptoms

with symptoms



Inhibit cox enzymes



  • Reduce prostaglandin production- less inflammatory mediators
  • Unopposed leukotrione action
  • Antipyretic effects – partly due to a decrease in prostaglandin that is responsible for elevating the hypothalamic set point for temp control in fever
cox enzyme
COX enzyme
  • Cyclo-oxygenase (COX) has two forms
  • COX-1 : protects the stomach lining from harsh acids and digestive chemicals. It also helps maintain kidney function
  • COX-2 : is produced when joints are inflamed or injured
  • Different NSAID’s inhibit the enzyme by different mechanisms
  • Aspirin – binds covalently with a serine residue of the enzyme (irreversible)
  • Ibuprofen/Piroxicam – reversible competitive inhibitors of COX non selective
  • Paracetamol – acts partly by reducing cytoplasmic peroxidase
older nonselective nsaid s ibuprofen naproxen
Older nonselective NSAID’s (Ibuprofen, Naproxen)
  • Block both COX-1 and COX-2, GI upset, bleeding as well as decreasing inflammation
  • Advice patients to take them with food or a glass of milk and should avoid alcohol.
  • Pros:
    • OTC version of these drugs are inexpensive
    • Low doses of aspirin taken over long term helps to prevent heart attacks, strokes and bowel cancer
  • Cons:
    • GI upset ie nausea, ulcers
    • Kidney problems from overuse
    • Interacts with warfarin
cox 2 inhibitors celecoxib meloxicam etorocoxib
COX-2 inhibitors (Celecoxib, meloxicam, etorocoxib)
  • Target only the COX-2 enzyme that stimulates the inflammatory response
  • Pros :
    • less likely to cause GI upset compared to the older NSAID’s
    • longer lasting drug – longer relief
    • do not thin the blood therefore can consider co-prescription with warfarin
  • Cons:
    • More expensive compared to traditional NSAID’s
    • Results not as good as endoscopic drug studies suggest
  • Commonest use – arthritis ie RA or OA and gout
  • Back pain, sciatica, sprains and strains and rheumatism
  • Dental pain
  • Post op pain
  • Period pain
  • Renal/ureteric colic
  • Fever
  • migraines
  • Elderly
  • Pregnancy- miscarriage, early closure of ductus arteriosus
  • Breast feeding
  • Coagulation defects
  • Renal, cardiac (heart failure/ hypertension/ IHD) or hepatic impairment
  • Severe heart failure
  • COX-2 : IHD, stroke, PVD and moderate to severe heart failure
  • CSM advice – previous or active peptic ulceration
  • hypersensitivity to aspirin or any NSAID – which includes those in whom attacks of asthma, angioedema, urticaria or rhinitis have been precipitated.
side effects
  • GI – N&D, dyspepsia bleeding and ulceration,
  • Hypersensitivity
  • Headaches, dizziness, nervousness, depression, drowsiness, insomnia, hearing disturbances
  • Photosensitivity
  • Fluid retention (heart failure), raise blood pressure
  • Hepatic damage, pancreatitis
  • Eye and lung changes (alveolitis)
  • Stevens-Johnson syndrome & toxic epidermal necrolysis (rare)
  • Similar anti inflammatory effects of selective and non selective NSAIDs
  • Non selective:
    • 15-40% dyspepsia, nausea, abdo pain
    • 10% discontinue
    • Severe GI toxicity 4.5/100pt years
  • Selective Cox 2 inhibiters
    • Similar GI symptoms
    • < 6% discontinue
    • Severe toxicity 2.1/100 pt years

NNT 42 to prevent 1 serious GI event

cardiovascular toxicity
Cardiovascular toxicity
  • Increased cardiovascular risk of selective NSAIDs is a problem
  • unopposed pro-thrombotic effects of COX-1-mediated production of thromboxane A2
  • Also, coxibs effects on blood pressure and renal function could turn out to be more detrimental than those of conventional NSAIDs.
cv risk
CV risk
  • It is a real risk ‘APPROVE’ study
  • Data obscured by clinical trials not recruiting ‘normal pts’
  • Data obscured by drug company manipulation of the results of clinical trials
  • Up to 42% higher risk of MI with selective
    • 0.6%/yr vs 0.3%/yr
all nsaid cvs
  • Rise in BP 3-5mm
  • Equate with an increase
    • CCF 10-20%
    • CVA 20%
    • Angina 12%

Lowest risk of all with naproxen (aspirin like effects)

  • Pain and inflammation in rheumatic disorders
  • 0.5-1g / day in 1-3 divided doses
  • In high risk pts, give with PPI
  • Which one?
nsaids past strategies
NSAIDs - past strategies
  • Enteric Coating
  • Pro-drugs; hepatic metabolism
  • Gastro-protective agents:PPIs, misoprostol, H2 blockade
oa adjunctive therapy
OA- Adjunctive therapy
  • Intra articular steroids plus local anesthetic for joint inflammation
  • Decrease production of inflammatory mediators
  • Can last a 3-6 months; use with physio
  • Probably can be done safely up to four times a year
    • not too frequently; can effect the cartilage
visco supplementation
  • Crosslinked hyaluronic acid polymers
  • OA (knee)
  • Intra-articular injections X 3-5
  • Change viscosity in joint
  • Pain relief with improved mobility
  • Success rate is 50-70% for up to 4-6 months
  • no systemic SE
visco supplementation1
  • OA, where physio, weight loss, simple analgesia +/- NSAIDs insufficient
  • & IA steroids not helpful /not lasting
  • Awaiting/ unfit for surgery
capcaisin cream
Capcaisin cream
  • 0.025% preparation (Zacin)
  • Depletes Substance P from nerve endings
  • Slow to act (1/12 to max effect)
  • More effective than topical NSAIDs
  • May reduce analgesic requirement
what are the alternatives
What are the alternatives?
  • Cod liver oil & other fishy oils
  • Evening primrose oil
  • Borage or Starflower oil
  • Change in balance of cell membrane fatty acids
  • Glucosamine 1.5 gram/day
    • substrate for glucosaminoglycans
    • Pain relief & mobility
  • Possible 10-25% analgesic effect
  • -disease modifier ?
  • ? Nutrition for cartilage
  • ? Stimulate metabolism
  • Vitamin C
  • Framingham study results show reduced pain OA of knee & hip
  • may improve integrity of cartilage
  • Joint inflammation caused by uric acid crystal deposits in the joint space
  • Primary
    • Over production (10%)
    • Under secretion (90%)
    • Enzyme mutations
  • Predominantly secondary
    • Overproduction (mutations, heavy exercise, obesity)
    • Under excretion severe renal diseases, drugs, alcohol, HBP
2-17% of population are hyperuricaemic
  • The higher the uric acid the higher the chance of gout
  • Self reported adult prevalence of 8/1000
  • 2-7M:1F
  • Increase in blacks may reflect increased rates of hypertension

Figure 4 Simplified diagram of uric acid production and excretion





Roddy E et al. (2007) The changing epidemiology of gout

Nat Clin Pract Rheumatol3: 443–449 doi:10.1038/ncprheum0556

  • Middle aged men
  • Dietary purine consumption
  • Alcohol
  • Drugs:Low dose aspirin, diuretics
  • Inherited metabolic abnormalities
clinical features
Clinical features
  • Gouty Tophi on pinnae
  • Olecranon bursitis
  • Gouty tophi on hands
  • Gouty nephropathy&


  • Large joint oligoarthritis
  • 1st metatarsophalangeal

joint arthritis‘podagra’

  • Prevent occurrence
  • Diagnose
  • Treat acute flare
  • Reduce risk of further flare
  • Reduce associated morbidity secondary to HBP, hypercholesterolaemia
aspirate joint
Aspirate joint
  • Differential diagnosis monoarthritis?
management of acute gout 1
Management of Acute Gout (1)
  • Goal is to rapidly resolve pain and inflammation
  • High doses of NSAID used:

Naproxen. 500mg bd until theattack has passed

Indomethacin, diclofenac, etoricoxib also used

management of acute gout 2
Management of Acute gout(2)

Alternative to NSAIDs


inhibits microtubule polymerization by binding to tubulin,

inhibition of neutrophil motility and so produces an anti-inflammatory response.

  • Colchicine 500mg bd to tds
    • 2/3 will respond cf 1/3 placebo
    • peak plasma concentration 1-2 hrs and a half life of 4 hrs
    • Metabolised by the liver with possible enterohepatic circulation
    • 20% excreted unchanged in urine
    • Avoid IV
    • Good alternative for patients receiving anticoagulants/patients in heart failure (doesn’t induce fluid retention) or those who cannot tolerate NSAIDs for any other reason
side effects colchicine
Side effects colchicine
  • GI
  • Haemorrhagic gastroenteritis
  • Myoneuropathy on prolonged course
acute gout treatment cont
Acute gout treatment cont.
  • NSAIDs- take early
    • Upper limit of usual therapeutic dose
    • Selective and non selective
  • Glucocorticoids
    • Intra-articular
    • Oral pred
    • IM pred
management of chronic gout 1
Management of Chronic Gout(1)
  • When is gout ‘ chronic’?
  • Recurrence of acute attacks, presence of tophi, or signs of gouty arthritis may call for preventative treatment.
  • Urate lowering therapy has been shown to be cost effective in patients with 2/more acute attacks/ year
management of chronic gout
Management of chronic gout
  • Decision to treat
    • Number of attacks
    • The uric acid level
    • Presence of reversible risk factors
    • Tophi
    • Renal impairment

Aim to reduce uric acid to below 0.36mmol/l or lower in the presence of tophi

choice of drug
Choice of drug
  • Decrease uric acid production by inhibiting xanthine oxidase
    • Not used in a history of hypersensitivity
  • Promote renal excretion of urate: uricosurics
    • Not useful if decreased GFR or history of renal colic
management of chronic gout allopurinol
Management of Chronic GoutAllopurinol

Allopurinol: 1st line therapy for Chronic Gout

Xanthine Oxidase inhibitor

Uric acid formation

  • Not to be started in the acute phase
  • Start 2-3 weeks following acute phase.
  • Initiation of allopurinol treatment may trigger acute attackstart with NSAID or colchicine & continue for 1 month after hyperuricaemia is corrected
management of chronic gout allopurinol dose
Management of chronic goutAllopurinol Dose
  • Initial 100mg OD ( Preferably after food)
  • Then adjusted accordingly to plasma/urinary uric acid levels:
  • Mild: 100-200mg daily
  • Moderately severe: 300-600mg daily
  • Severe: 700-900mg daily

Doses> 300mg should be given in divided doses

management of chronic gout allopurinol ctd
Management of Chronic GoutAllopurinol ctd


  • Hepatic impairment
  • Renal Impairment
  • Pregnancy
  • Breast Feeding


  • Acute gout!
  • Side effects ( extensive list in BNF)
  • Rashes: Withdraw therapy(if mild re start but withdraw immediately if reccurs)
  • Neuropathy
  • Blood disorders
  • Renal impairment
  • Hepatoxicity
  • High dose aspirin (note low dose retains urate)
  • Sulfinpyrazone
  • Probenecid
  • Benzbromarone
    • Use colchicine prophylaxis
    • Slowly increase dose
    • Alkaline diuresis with water loading and oral bicarb
management of chronic gout 5 sulfinpyrazone
Management of Chronic gout (5)Sulfinpyrazone
  • A uricosuric drug – increases the excretion of uric acid
  • Used instead of allopurinol, or in conjunction.
  • Dose 100-200mg daily, increasing over2-3 weeks to 600mg(rarely 800mg) daily, until serum uric acid levels normal.


  • Hepatic impairment
  • Renal impairment
  • Pregnancy


  • in patients with a history of hypersensitivity to aspirin or any other NSAID—which includes those in whom attacks of asthma, angioedema, urticaria or rhinitis have been precipitated by aspirin or any other NSAIDs)
  • coagulation defects
  • Hx of MI/Stroke or PAD
  • moderate or severe heart failure
  • active pepticulceration
also address
Also address…
  • Obesity
  • Triglycerides
  • Alcohol
  • Hypertension
  • Thiazide therapy- consider alternative
ra psoriatic arthritis
RA (& Psoriatic Arthritis)
  • 600,000 people in UK
  • many unable to work
  • 42% registered disabled within 3 years
  • 80% moderate to severe disability in 20 years


  • Physiotherapy & OT very important
    • must see early or lose mobility quickly
    • Range of motion, exercise & how to protect joints
  • NSAIDs
  • consider low-dose corticosteriods (suppress symptoms while DMARDSs have time to work)
5-10% very aggressive disease

60% moderate

severe disability, co-morbidity, reduced life expectancy, despite conventional therapy

Large burden on hospital & social services, carers

Successful reduction disease progression may reap long term cost savings

e.g. Reduction in need for joint replacement

dmards what are they
DMARDS: What are they?
  • Disease -modifying antirheumatic drugs, (used in other chronic inflammatory diseases as well)
  • DMARDs influence the disease process, unlike NSAIDs which just alleviate symptoms
  • varying and sometimes poorly understood mechanisms of action
  • e.g. methotrexate, sulfasalazine, gold compounds, penicillamine, chloroquine and biologic agents- which target the action of TNF alpha
current treatment
Current Treatment
    • Early & Aggressive
  • Sulphasalazine, Methotrexate, Cyclosporin, Leflunomide, (IM Gold)
  • Single or combination Rx
ra psa
  • Others (D-penicillamine, azathioprine, hydroxychloroquine)
  • More aggressive (cyclophosphamide, mycophenolate)
  • Any/ all may be ineffective + /or toxic
  • dihydrofolate reductase inhibitor/ folate antagonist – purine antagonist
    • dihydrofolate reductase reduces folate to FH4, the latter being an essential co-factor in DNA synthesis)
  • uses: RA (1st line DMARD), psoriasis (if severe/ resistant to topical treatments), cancer, Crohn’s disease
CI: severe blood disorders, active infections, immunodeficiency, kidney or liver failure, pregnancy (females and males must avoid conception for at least 3/12 after stopping treatment), breast-feeding
  • cautions: effusions (especially ascites and pleural effusions as these act as ‘storage’ for the drug thereby increasing its toxicity), UC, peptic ulcer, decreased immunity and prophyria
Se: mucositis/ GI upset, myelosuppression, skin reactions. Rarely: pulmonary fibrosis/ pneumonitis, hepatotoxicity, neurotoxicity, seizures, renal failure (due to precipitation of the drug in the renal tubules)
  • interactions: NSAIDs (caution), trimethoprim, co-trimoxazole. These increase toxicity levels
dose: methotrexate is usually given orally but can be given im or subcut (intrathecally- only in oncology)
  • 7.5mg onceWEEKLY
  • max 25mg/week.
Pre-tx assessment:
  • FBC, U&E's, creatinine, LFT's, CXR.


  • FBC fortnightly- until 6/52 after last dose increase, and provided it is stable monthly thereafter.
  • LFT's fortnightly
  • U&E's 6-12 monthly (more frequently if there is any reason to suspect deteriorating renal function).
Action to be taken (i.e. discuss with rheumatologist) if:
  • WBC <4.0x10^9/l, neutrophils<2.0x10^9
  • Platelets<150x10^9 /l
  • >2-fold rise in AST, ALT (from upper limit of reference range)
  • Unexplained fall in albumin
  • Rash or oral ulceration
  • New or increasing dyspnoea or cough
  • MCV>105fl (investigate and if B12 or folate low start appropriate supplementation)
  • Significant deterioration in renal function
  • Abnormal bruising or sore throat
note that in addition to absolute values for haematological indices a rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance.
sulphasalazine en
Sulphasalazine (EN)
  • 1st or 2nd choice in UK; mild to moderate
  • not teratogenic or strong immunosupressant
  • Up to three months to take effect
  • GI SE, elevated LFTs, bone marrow depression
  • Monitoring bloods 3 monthly
  • first introduced for antibiotic action in colon, for inflammatory bowel disease.
  • mode of action unclear - ?anti-inflammatory, immunomodulatory and/or antibacterial
  • start early to tide over or adjunct e.g. to MTX
  • Prednisolone
    • Modest dose (7.5-10 mg/day) & decrease
    • Long term dose should not exceed 10 mg/day
    • Treat acute flares IA IM or IV
  • SE:
    • Wt gain, Cushings, bruising, osteoporosis, infection risk
    • Discontinuation may be difficult
gold therapy
Gold therapy
  • Established> 50 yrs as effective treatment
  • weekly painful injection for 6/52 then 2-4 /52
  • freq lab monitoring; BM suppression; nephritis
  • Decreases phagocytosis & monocyte activation
  • Inhibits lymphocyte responses
  • SE
    • 35% discontinue
    • rash & stomatitis
    • proteinuria
    • glomerulonephritis
cyclosporin a
Cyclosporin A
  • Nephrotoxicity espec with NSAIDs
  • causes hypertension
  • usually in combination
  • Azathiaprine
  • moderate efficacy, three months to reach efficacy
  • purine antagonist, & interferes with nucleotide synthesis
  • SEs liver toxicity, bone marrow toxicity, monitoring 3/12
    • Cyclosporin & azothiaprine used in 2-5% of pts
  • pyrimidine antagonist
  • comparable efficacy to SZP
  • probably comparable toxicity
  • may be tolerated/ effective where other drugs not suitable
  • after methotrexate, before CyA
mycophenolate mofetil
Mycophenolate Mofetil
  • Reversible inhibitor inosine monophosphate dehydrogenase
  • inhibition lymphocyte proliferation/ antibody formation/ adhesion molecule expression
  • Improved safety cf. other immunosupressants
  • SLE nephritis;refractory to cyclophosphamide
  • Scleroderma.
  • (RA)
biological therapy anti tnfs
Biological therapy: Anti-TNFs
  • anticytokine therapy
  • specifically target TNF-alpha, which is an important mediator of rheumatoid inflammation
  • uses: RA, psoriatic arthritis and ankylosing spondylitis
  • current guidelines (developed by the British Society for Rheumatology in 2003) restrict their use in the UK to patients who fail two or more conventional second-line agents
pre administration
  • Disease Activity Score (DAS) of joint count on two occasions (one month apart) before treatment
  • Pre-tx: bloods (FBC, U&E, LFT, ANA and DNA binding), check for TB, do not administer live vaccines, check cardiac function and demyelinating diseases (b/c these are all side-effects of medication)
  • for subcutaneous self-administration – assess patient’s ability to self-administer; include training plan
adalimumab infliximab etanercept
Adalimumab, Infliximab & Etanercept
  • monoclonal antibody against TNF-alpha or fusion protein against soluble TNF alpha
  • MOA/ a TNF receptor joined to the Fc domain of a human IgG molecule (basically acts to mop up TNF molecules taking them ‘out of circulation’).
  • CI/ pregnancy, breastfeeding, severe infections.
  • Severe infections- TB, septicaemia
biological therapy b cell depletion e g rituximab
Biological therapy: B-cell depletion, e.g. Rituximab
  • a monoclonal antibody against CD20 which causes lysis of B-cells
  • uses/ lymphoma chemotherapy, RA.
  • used with methotrexate in patients who have had an inadequate response to the anti-TNFs.
  • MOA/ binds to CD20 molecule on the B-cell.
  • BNF
  • various pharmacology books and websites..
psoriatic arthritis
Psoriatic arthritis
  • 10% with psoriasis get psoriatic arthritis.
  • Often asymmetrical inflammatory arthropathy
  • NSAIDs & Sulphasalazine in early stages, but neither affects the psoriasis.
  • Methotrexate, CyA & anti-TNF drugs treat both the arthritis & the psoriasis
ankylosing spondylitis
Ankylosing spondylitis
  • DMARDS dismal in treating axial disease
  • NSAIDs for pain & stiffness
  • Exercise & physio
  • Sulphasalazine, & Methotrexate particularly useful with peripheral disease
  • Anti-TNF drugs for axial disease

Common, preventable, potentially disabling

Worth treating to prevent further #, & improve quality of life

Primary Care


Socioeconomic Costs Osteoporotic Fractures

  • 200,000 osteoporotic fractures each year cost NHS an estimated £1.5 billion
  • 1 in 2 women experience a fracture by the age 70.
  • 1 in 12 men at risk of fracturing due to osteoporosis at some time in their life.



Attainment of Peak

Bone Mass


Age Related Bone Loss






0 10 20 30 40 50 60

Age (years)

Age Related Changes in Bone Mass1



1. Compston JE. Clinical Endocrinology 1990; 33: 653-682.


Osteopaenia: T score <-1-<2.5
  • Osteoporosis ; T score <-2.5
  • T score means comparing the pts density to a 25 year old female.
identifying those at risk
Identifying those at risk
  • Predisposing factors-
    • alcohol, smoking
    • liver or renal disease
    • malabsorption, poor Ca intake
    • Low BMI
    • thyroid disease, DM, Cushings, hyperparathyroidism
    • immobility, inflammatory disease, RA
    • hypogonadism in men
identifying those at risk1
Identifying those at risk
  • drugs
    • Current or planned long term oral corticosteroid use (>7.5mg prednisolone / day for > 3/12
    • Anticonvulsants
    • heparin
management 1 patient education
Management 1. Patient Education
  • Lifestyle Changes: Diet Weight bearing exercise Habits: smoking & excess alcohol
  • Falls Prevention home assessment hip protectors
nice guidance 1
NICE guidance 1
  • Primary prevention
  • Complex
  • >70 with a risk factor for fracture or an indicator for fracture and t score <-2.5
nice 2
  • Secondary prevention ie at least 1 fracture Ca + vit D
  • >75yrs bisphosphonate
  • 65-74 DEXA< and if <2.5 then bisphos
  • <65 treat if T score < -3, or -2.5 plus a risk factor
nice 3
  • Prevention of steroid induced OP:
  • Lifestyle advice
  • Ca & vit d
  • <65 yrs DEXA, bisphosphonate if osteopaenic
  • >65 bisphosphonate
osteoporosis pharmacology
Osteoporosis Pharmacology




Raloxifene & Teriparatide

Vitamin D

Calcium salts

  • Indications: Osteoporosis, ↓Ca2+, ↑ PO4
  • Contraindications: Conditions associated with ↑Ca2+
  • Side effects: GI disturbances, arrhythmias, bradycardia
  • Interactions: effects potentiated by thiazides and decreased by corticosteroids. Decreases absorption of tetracyclines and biosphosphonates.
  • In osteoporosis, calcium intake double recommended amount reduces rate of bone loss.
  • Dose: 400-800mg/ day
    • Adcal D3 forte, calcichew D3 Forte
vit d
Vit D
  • Examples: ergocalciferol, calciferol, cacitriol
  • Mechanism of action: stimulates absorption of calcium and phosphate from intestine and decreases renal excretion of calcium
  • Indications: Osteoporosis, CRF, osteomalacia, hypoparathyroidism
  • Side effects: Vascular calcification, nephrocalcinosis, soft-tissue calcification
bisphosphonates pharmacology
Bisphosphonates Pharmacology
  • Alendronate and residronate orally, pamidronate, ibandronate and zoledronate IV
  • Mechanism of action: inhibit osteoclastic activity. Specifically reduce the resorption and formation of hydroxyapatite crystals.
  • Indications: postmenopausal osteoporosis, paget’s disease of bone, malignancy-associated hypercalcaemia
  • Adverse effects: bone pain, osteomalacia (etidronate), oesophagitis, nausea, diarrhea
  • 70mg alendronate once a week with ca and vit d
raloxifene evista
Raloxifene (Evista)
  • Selective oestrogen receptor modulator (SERM) treatment / for prevention of postmenopausal osteoporosis
  • Demonstrates oestrogen agonist activity on bone & partially on cholesterol metabolism, but oestrogen antagonism in uterine and breast tissues.
  • ? Benefits in stroke and breast cancer reduction
strontium ranelate protelos
Strontium ranelate (Protelos)
  • granules for oral suspension
  • treatment of postmenopausal osteoporosis
  • As good as bisphosponates & well tolerated (even in very elderly)
  • Increases bone formation & decr bone resorption
  • Absorption affected by food & milk/derivatives.
  • Suspension should ideally be given at bedtime, at least two hours after any food drink
  • cost per month comparable with branded bisphosphonates & raloxifene.
  • Synthesised and secreted by parafoliicular C cells of thyroid gland
  • Mechanism of action: decreases osteoclastic bone resorption and calcium and phosphate resorption from kidney.
  • Indications: osteoporosis, paget’s disease of bone, malignancy-associated hypercalcaemia
  • Adverse effects: allergic reaction (flushing, redness or tingling of face), nausea, increased urinary frequency
  • Dose: for postmenopausal osteoporosis: 200 units (1 spray) intranasally
teriparatide rdna foresteo
Synthetic parathyroid hormone; 5X greater BMD in lumbar spine than alendronate after 6/12

BUT daily injections with 20mg Forteo for 18/12

Teriparatide 20mcg daily - 1 prefilled pen = £271.88

Raloxifene 60mg daily = £21.74

Fosamax once weekly 70mg = £23.12

stimulates new bone formation

teriparatide rDNA (Foresteo)
teriperatide cont
Teriperatide cont
  • animal studies increased incidence osteosarcoma
  • Can use for secondary prevention if >65 and bisphosphates not helpful and T score <-4
  • Fully human monoclonab antibody to RANK ligand
  • RANK is expressed by pre-osteoclasts, and induces their conversion into mature osteoclasts
  • There for inhibits clasts, reducing bone resorption
  • Sub cut every 6 months
  • Cost similar to branded bisphosphonates
  • Plenty of hope with new treatments
  • BUT
  • Also plenty of
  • a) COST &
  • b) scope for causing harm