Treatment of major rheumatic diseases
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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

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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

  • 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

  • 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

  • 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

  • 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)

  • 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)

  • 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.


  • 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

  • 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

  • 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


  • 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

  • Enteric Coating

  • Pro-drugs; hepatic metabolism

  • Gastro-protective agents:PPIs, misoprostol, H2 blockade

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


  • 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


  • OA, where physio, weight loss, simple analgesia +/- NSAIDs insufficient

  • & IA steroids not helpful /not lasting

  • Awaiting/ unfit for surgery

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?

  • 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

  • Gouty Tophi on pinnae

  • Olecranon bursitis

  • Gouty tophi on hands

  • Gouty nephropathy&


  • Large joint oligoarthritis

  • 1st metatarsophalangeal

    joint arthritis‘podagra’

erosions with a punched out appearance


  • Prevent occurrence

  • Diagnose

  • Treat acute flare

  • Reduce risk of further flare

  • Reduce associated morbidity secondary to HBP, hypercholesterolaemia

Aspirate joint

  • Differential diagnosis monoarthritis?

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)

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

  • GI

  • Haemorrhagic gastroenteritis

  • Myoneuropathy on prolonged course

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)

  • 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

  • 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

  • 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 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 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 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

  • 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…

  • Obesity

  • Triglycerides

  • Alcohol

  • Hypertension

  • Thiazide therapy- consider alternative


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?

  • 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

  • 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)

    • 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

    • 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

    • 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

    • 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

    • 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


    • 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

    • 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

    • 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

    • 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

    • 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

    • 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 risk

    • drugs

      • Current or planned long term oral corticosteroid use (>7.5mg prednisolone / day for > 3/12

      • Anticonvulsants

      • heparin

    Management 1. Patient Education

    • Lifestyle Changes: Diet Weight bearing exercise Habits: smoking & excess alcohol

    • Falls Prevention home assessment hip protectors

    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

    • >65bisphosphonate

    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

    • 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

    • 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)

    • 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)

    • 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

    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

    • 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

    • Questions?

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