osteoporotic back pain

Osteoporosis

Consirable cause of back pain

2015

Back Pain2nd most common cause for office visit60-80% of population will have lower back pain at some time in their livesEach year, 15-20% will have back painMost common cause of disability for persons < 45 years1% of US population is disabledCosts to society: $20-50 billion/year

3/4/03Steven Stoltz, M.D.

Low Back Pain“One would have thought by now that the problem of diagnosis and treatment would have been solved, but the issue remains mysterious and clouded with uncertainty.”

– Rosomoff HL, Rosomoff RS. Low back pain: Evaluation and management in the primary care setting. Med Clin North Am 1999;83:643-62.



- AnatomyLesson #1


- AnatomyLesson #2

% of Back Pain due to Herniated Disk?

1. 4%2. 14%3. 40%4. None of the above


Causes of Low Back PainLumbar “strain” or “sprain” – 70%Degenerative changes – 10%Herniated disk – 4%Osteoporosis compression fractures – 4%Spinal stenosis – 3%Spondylolisthesis – 2%


Causes of Low Back Pain…Spondylolysis, diskogenic low back pain or other instability – 2%Traumatic fracture - <1%Congenital disease - <1%Cancer – 0.7%Inflammatory arthritis – 0.3%Infections – 0.01%


Steven Stoltz, M.D.

Red Flags

History of cancerUnexplained weight lossIntravenous drug useProlonged use of

corticosteroidsOlder age

Major TraumaOsteoporosisFeverBack pain at rest or at

nightBowel or bladder

dysfunction

3/4/03

10

What is osteoporosis?• Bones are fragile and more likely to

break (or fracture) easily

• Fractures = broken bones

• Fragility fractures occur with minimal trauma

• Fractures can lead to pain, changes in body shape and disability

11

Healthy bone Osteoporotic bone

The Living Skeleton

Changes in bone mass with age

Bone mass

Age (years)

Women

0 10 20 30 40 50 60 70 80

• Nutrition?• Vitamin D in the womb

Adapted from J Compston 1990

Menopause

Peak bone mass • Age related bone loss• Reduced physical activity

• Genes• Nutrition• Exercise

Men

15

Common fracture sites

Wrist Compressedvertebrae in spine

Hip

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Vertebral compression fractures (multiple and severe)• Back pain – acute and chronic

• Height loss and curvature

• Activities of daily living affected; eating, breathing and mobility

© IOF developed with Prof. Dieter Felsenberg for Stop the Stoop campaign

17

A broken hip can lead to serious disability

Cooper. 1997

Unable to walk independently

Difficulty with daily activities

Restricted driving & shopping

Admitted to nursing home

0 20 40 60 80 100% affected within 1yr

18

The impact of fractures on health and social services

Every year in the UK:

• 300,000 osteoporotic fractures

• Over £2.3 billion per year on hospital and social care costs for hip fracture alone -

(approx. £6 million/day)

PATHOPHYSIOLOGY

HALLMARK: reduced skeletal mass due to imbalance btn bone resorption and formationFailure to build bone reserve from childhoodBone lossAging with loss of gonadal functionBone loss accelerates rapidly in women during the first years after menopause

a) Estrogen deficiency leads to…

↑ expression of RANKL by osteoblasts↓ release of OPG↑recruitment of pre-osteoclasts→↑differentiation and prolonged survival of osteoclasts via IL-1,IL-6,TNFᾳ.T-Cells inhibit osteoblastic differentiation and activity with premature apoptosis of osteoblasts through cytokines e.g. IL-7

Increased sensitization of bone to the effects of PTH↑osteoclastic apoptotic activity via ↑production of TGFᵝ

b) Aging

Progressive ↓ in supply of osteoblasts Reduced Ca2+ uptake from GITBone resorption exceeds bone formation from 3rd decadeWomen lose-30-40% of cortical bone -50% of trabecular boneMen lose-15-20% of cortical bone -25-30% of trabecular bone

c) Ca²⁺deficiency

→2° hyperPTH -↓ renal excretion of Ca2+ -↑ renal production of 1,25-(OH)2-D (calcitriol)→↑ca2+ absorption from the gut →↑bone resorption

d) Vit D Deficiency

Impaired absorption of Ca2+ from gutCompensatory mechanism:-Leads to hyperPTH→↑production of calcitriol from the kidneysPTH and vit.D have their effect on bone being mediated via binding to osteoblasts and stimulating RANK/RANKL pathwayOsteoclasts do not have receptors for Vit.D or PTH

Osteoporotic Fractures

Insufficiency/ fragility fracturesMostly from low-energy trauma/minor loadsVertebral bodies-1rly cancellous with interconnected horizontal and vertical trabeculae.

In osteoporosis there’s ↓ in both bone mass and this internal interconnectivity(BUT preferentially disruption is in the horizontal trabeculae)→? Reason→?overaggresive osteoclastic resorption

26

How do I know if my bones are fragile?

Signs and symptoms:

• Osteoporosis is painless unless bones break (fracture)

• Fragile bones may break easily without too much force

• Significant height loss and curvature of the spine may indicate compression fractures

27

How do I know if my bones are fragile?

• Risk factors will make fragile bones more likely

• A bone density scan will indicate if bones are less dense than average, but it is not needed by everyone

28

Risk factors for osteoporosis and fractures

• Age• Race• Gender• Some medicines -

e.g. glucocorticoids (‘steroids’), breast and prostate cancer drugs

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Risk factors (continued) • Some medical conditions e.g. rheumatoid arthritis and early

menopause

• Medical conditions causing immobility, affecting food absorption, or affecting hormone levels

• Low body weight

• Family history

• Current smoking

• Alcohol more than 3 units daily

• Bones have already broken easily

Vertebral compression fractures

2/3 are asymptomatic and occur slowlyAssociated with ↑morbidity and mortalityMortality also correlates with number of vertebral #Often occurs with minimal stressMostly affected-middle/lower thoracic and upper lumbar

As posture worsens and kyphosis progresses→difficulty with balance, back pains, resp. compromise,↑ risk of pneumonia

↓ QOL

Presence of a # at one vertebral level→5-fold ↑ risk of getting another

CLINICAL PRESENTATIONS

Episode of acute back pain after bending, coughing,lifting, a fall, minor traumaPain-sharp, nugging, dull; exacerbated by movt; may radiate to the abdomen

Progressive kyphosis with loss of height+/- localised painParavertebral muscle spasm exacerbated by activity/ reduced by lying supine.

Complications:

Chronic pain↑morbidity and mortality↓ QOLProlonged immobilitySevere kyphosisSpinal deformities→”dowager’s hump”→loss of 1-2’ of height by 7th decade of lifeLoss of self-esteem→depression

PHYSICAL EXAM

InspectionPalpationHeight measurementActive/passive ROMNeurological exam

DDX

OsteomalaciaTumors(osteolytic)InfectionsOsteonecrosisOther bone-softening metabolic disorders Leukaemia/lymphomaOsteogenesis imperfectaRenal osteodystrophyMultiple myelomaScurvyPaget’s diseaseSickle cell anaemiaHomocystinuria/homocystinaemia

WHO-Fracture-Risk algorithm(FRAX)

Developed to calculate 10yr probability of any major osteoporotic # in a given patientTake into a/c BMD and other clinical risk fxtrsNOF recommends RX for patients with WHO-10yr-probability of major osteoporosis-related # of >20% (or >3% for hip #)This algorithm is useful in identifying patients most likely to benefit from Rx.

Fracture risk estimation

SCREENING

Women >50yrs of ageFor men, not carried out routinelyUS preventive Services Task Force(USPSTF)/ American College of Physicians(ACP) recommendations:Indications for screening in menThose with 10yr risk for osteoporotic # equal to or greater than that for 65yr old women who have no additional risk factors

INVESTIGATIONS

i) LAB WORKUPa) To establish baseline conditions:-CBC-Serum Ca²⁺,mg²⁺,po4-,Fe2+/ferritin levels-LFTs-TFTs-Vit. D levels-Cr/BUN

b) To exclude 2° causes

24 hr-urinary Ca2+ levelsPTH levelTestosterone/gonadotropin levelESR/ CRPUrinary free cortisol levels/ dexamethasone suppression testBMASerum/Urinary protein electrophoresis

ii) Biochemical markers of bone turnover

Reflect bone formation and resorption

Maybe ↑in high-bone turnover states and may also be useful in some patients for monitoring early response to treatment

SERUM MARKERS OF BONE FORMATION

Bone specific alkaline phosphatase(BSAP)Osteocalcin(OC)-if high, indicates a high turnover osteoporosisCarboxyterminal propeptide of type 1 collagen(PICP)Aminoterminal propeptide of type 1 collagen(PINP)

SERUM MARKERS OF BONE RESORPTION

Cross-linked C-Telopeptide of type 1 collagen(ICTP)Tartrate-resisitant acid phosphataseN-Telopeptide of collagen cross-links(NTx)C-telopeptide of collagen cross-links(CTx)

URINARY MARKERS OF BONE RESORPTION

HydroxyprolineFree and total pyridinolines(Pyd)Free and total deoxypyridinolines(Dpd)NTxCTx

46

Diagnosis OSTEOPOROSIS

-Measurement of BMD or-Occurrence of adulthood hip or vertebral fracture in the absence of major trauma

• Excellent diagnostic tools– Bone densitometry with DXA –

noninvasive test

– FRAX® – new tool to help with management decisions in patients with reduced bone mineral density

• Effective and safe treatments

National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013. Available at: http://www.nof.org/hcp/clinicians-guide. Accessed September 13, 2013.

Z- and T-scores in Women

48

Who should be tested?

BMD measurement is not recommended in children or adolescents and is not routinely indicated in healthy young men or premenopausal women unless there is a significant fractures history or there are specific risk factors for bone loss

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Consider vertebral imaging tests for the following individuals:

All women age 70 and older and all men age 80 and older if BMD T-score at the spine, total hip or femoral neck is < -1.0.

Women age 65 to 69 and men age 70 to 79 if BMD T-score at the spine, total hip or femoral neck is < -1.5

Postmenopausal women and men age 50 and older with specific risk factors:

Low trauma fracture during adulthood (age 50) Historical height loss of 1.5 inches or more (4 cm)* Prospective height loss of 0.8 inches or more (2 cm)** Recent or ongoing long term glucocorticoid treatment

Vertebral Imaging

* Current height compared to peak height during young adulthood** Cumulative height loss measured during interval medical assessment*** If bone density testing is not available, vertebral imaging may be considered based on age alone

(b) Densitometry1) Dual-Energy X-Ray Absorptiometry(DXA)-quantifies bone loss-standard for evaluation of BMD-not as sensitive as QCT for detecting early

trabecular bone loss, but it provides rapid scanning times, is less costly and precise

-used to calculate BMD at the lumbar spine, hip, prox. femur and wrist

-data is reported as T and Z-scores

5) U/S

Quantitative U/S of the Calcaneus(QUS)

-The heel is the only validated skeletal site for clinical use of QUS in osteoporosis mx.

-low cost, no radiation

-not as accurate.

Osteoporosis diagnosed on a scan

Bone density scanning of hip and spine:dual energy X-ray absorptiometry (DXA)

53

Osteoporosis on a DXA bone density scan

-1 SD

-2.5 SD

NORMAL

LOW BONE MASS (OSTEOPENIA)

NO FRACTURE (OSTEOPOROSIS)

WITH FRACTURE(SEVERE OSTEOPOROSIS)

WHO Study Group 1994

54

Bone density (DXA) scanning

Useful:• For those with significant risk factors • when it is uncertain if bones are fragile• to decide whether drug treatment is

necessary

May be useful:• In those taking drug treatments • to see if a treatment is working (this may

not always be helpful)

Not useful:• As a ‘screening’ tool

56

How can the risk of fragility fractures be reduced?

Fragility fractures

Poor bone strengthFalls

(except fracturesin the spine)

Impact of fallslack of padding

LifestyleExercise

Healthy eatingSunlight

Healthy pregnancyNo smoking/ excessive alcohol

& Other interventions for falls prevention

Flooring,hip protectors

Drugs,including Vit D

57

What can I do to keep my bones strong and prevent fractures?

• Healthy, balanced, calcium-rich diet• Weight-bearing exercise• Maintain appropriate body weight• Not smoking• Not excessive alcohol• Adequate vitamin D

59

UK recommended daily calcium intake (mg): COMA report 1998

Children aged 7-12 years 550Teenagers – males 1000Teenagers – females 800Adult males 700Adult females 700Pregnant women 700Lactating women* 1250

A daily intake of about 1000mg may benefit those with osteoporosis on treatment, but excessive amounts taken as a supplement could be harmful

*May not be necessary

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Keeping steady and safe as we get older to prevent hip fracture

• Medical conditions – get them diagnosed and properly treated

• Medicines – get them checked Do you need them all? Get a Review

• Vitamin D – supplements?

61

Keeping steady and safe as we get older to prevent hip fracture

• Keep fit and active as you get older

• Specific exercises help to improve balance and muscle strength

• Tai Chi

• Safe home environment

• Hip protectors?

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Drug treatments: bisphosphonates• Alendronic acid or alendronate (Fosamax and

Fosamax once weekly)

• Risedronate (Actonel and Actonel once weekly)

• Ibandronate (Bonviva)*

• Zoledronate (Aclasta)*

63

Drug treatments: others • Raloxifene (Evista)

• Denosumab (Prolia)*

• Parathyroid hormone (PTH) - (teriparatide - Forsteo)*

• Strontium ranelate (Protelos)**

• Hormone replacement therapy (HRT)• Calcium and vitamin D supplements

• Calcitriol (Rocaltrol) (active form of vitamin D)

10-year risk of fractures: ≥3% for hip fracture

or ≥20% for a major osteoporotic fracture

T-scores between -1.0 and -2.5 and

NOF Guidelines 2014:Whom to Treat

After exclusion of secondary causes, treat postmenopausal women and men

age 50 and older who have…

OsteoporosisClinical diagnosis:

Hip or spine fracture

DXA diagnosis: T-score -2.5 or below

in the spine or hip

National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2014. Available at: http://www.nof.org/hcp/clinicians-guide..

Prevention Treatment

FDA-Approved Therapeutic Options

EstrogenAlendronateRisedronate

Ibandronate Zoledronic acid

Raloxifene

Calcitonin

PTH (teriparatide)Denosumab

US FDA Approved Therapies with Evidence for Fracture Prevention in Postmenopausal Women*

Type of Fracture

Antiresorptive therapyBone

formation therapy

Bisphosphonates(As first line therapy)

Calcitonin RaloxifeneHormone therapy

(Estrogen)**Teriparatide

Ibandronate,Risedronate, Alendronate, Zolendronic Acid

Vertebral Hip - - -

Non-vertebral+ - -

* For postmenopausal women, indicates first line therapies and Grade A recommendation. For men requiring treatment,alendronate, risedronate, and zoledronic acid can be used as first line therapies for prevention of fractures [Grade D]. + In clinical trials, non-vertebral fractures are a composite endpoint including hip, femur, pelvis, tibia, humerus, radius, and clavicle. ** Hormone therapy (estrogen) can be used as first line therapy in women with menopausal symptoms.

Ibandronate: Konsisten dalam mengurangi resiko fraktur vertebra

100

80

60

40

20

0

RR

R in

ver

tebr

al fr

actu

re (%

)

BONE study. Ibandronate 2.5mg daily vs. placeboChesnut CH, et al. J Bone Miner Res 2004;19:1241–1249

0–1 0–2 0–3Years

58%RRR p=0.0561

61%RRR p<0.001

62%RRR p<0.001

New Morphometric Vertebral FracturesData in: Chesnut CH, et al. J Bone Miner Res 2004;19:1241–9

10.750.50.25

Year 1

Year 2

Year 3

58%

61%

62%

Efficacy BONVIVA yang cepat dan konsisten dari waktu ke waktu

Year 1

Year 2

Year 3

10.750.50.25

65%

55%

41%

New Morphometric Vertebral FracturesRisedronate USPIHarris ST, et al. JAMA 1999;282:1344–52

BONVIVA® RISEDRONATE®

Alendronate(5/10mg)

Risedronate (5mg)

BONVIVA (2.5mg)

70

60

50

40

30

20

10

0

RR

R fo

r ver

tebr

al fr

actu

re a

t 3 y

ears

(%)

41%

VERT-NA3

62%70

60

50

40

30

20

10

0

BONE1

47%

FIT2 70

60

50

40

30

20

10

0

Efek Bisphosphonate pada fraktur new vertebral dalam 3 tahun

NOT COMPARATIVE STUDIES1Chesnut CH, et al. J Bone Miner Res 2004;19:1241–92Black DM, et al. Lancet 1996;348:1535–413Harris ST, et al. JAMA 1999;282:1344–52

VIBE STUDY

Ibandronate terbukti menurunkan resiko fraktur vertebra yang lebih tinggi dan menurunkan resiko fraktur non vertebra yang sebanding dengan Bisphosphonat mingguan

Mobile LTE: IBandronate meningkatkan BMD secara berkesinambungan hingga >5 tahun

Miller PD et al. Osteoporos Int. 2012 Jun;23(6):1747-56.

DIVA STUDY

BONVIVA IV TERBUKTI MEMPERTAHANKAN KENAIKAN BMD SELAMA 5 TAHUN

73 2013

Ibandronat IV memiliki insiden AE yang lebih kecil jika dibandingkan Zolendronat IV

DIVINE Study: Profil keamanan Bonviva® injeksi setara dengan BP oral

Miller PD et al. Bone. 2011 Dec;49(6):1317-22.

Patients expressing a preference, modified intent-to-treat (mITT)=298; 93% of population expressed preference between the two regimensEmkey R, et al. Curr Med Res Opin 2005;21:1895–903Hadji P, et al. Osteoporos Int 2006;17(Suppl.1):S69 (Abstract P259)

BALTO II

71% memilih once-monthly ibandronate(p<0.0001)

BALTO I and II menunjukkan positive preference dan kenyamanan

BALTO II77% considered

once-monthly ibandronate convenience

(p<0.0001)

BONVIVA: a bisphosphonatedengan potensi untuk meningkatkan kepatuhan

Cannot tolerate oral administration

Do not respondto oral therapy

The need for I.V. bisphosphonatesin osteoporosis

Cannot follow Dosing instructions

e.g. bedridden

Are takingmultiple oralmedications

Postmenopausal osteoporosis patients best suited for i.v. administration are those who

Have problems with adherence to oral bisphosphonates

i.v. = intravenous

Have cognitive difficulties

Have abnormalities delaying oesophageal

emptying

Bonviva Indication and Dosage Form

● Indikasi : Treatment of osteoporosis in postmenopausal women at increased risk of fracture. A reduction in the risk of vertebral fractures has been demonstrated, efficacy on femoral neck fractures has not been established.

● Sediaan:

MEKANISME KERJAIbandronate bekerja dengan cara : Menghambat aktivitas osteoklas Menghambat pembentukan osteoklas Menghambat pematangan ( maturation ) osteoklas

Adapted from : Russell RG, Rogers MJ. Bone 1999;25:97–106

● Hypocalcemia● Hypersensitive terhadap Ibandronic Acid

Kontraindikasi

●Hypocalcemia harus ditangani sebelum memulai terapi Bonviva diperlukan suplementasi Ca dan vitamin D yang cukup

●Tidak direkomendasikan untuk pasien dengan creatinine clearance di bawah 30 ml/min

●Tidak direkomendasikan untuk ibu hamil no adequate data

Special Warning (Peringatan)

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Living with broken bones: help after vertebral compression fractures - 1

• Pain relieving drugs• Physiotherapy and specific exercises• Corsets?? (short-term)• Hydrotherapy – warm water• Complementary therapies

e.g. acupuncture• Heat and cold / gentle massage

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Living with broken bones: help after vertebral compression fractures - 2• TENs machines

• Pain clinics / management courses

• Self management classes(e.g. Expert Patient)

• Percutaneous vertebroplasty / balloon kyphoplasty

• Charity’s website, publications and Helpline

83

Living with broken bones: help after a hip fracture • Effective assessment and operation to help with healing• Adequate pain relief • Physiotherapy and rehabilitation• Return to own home if at all possible• Appropriate social care• Osteoporosis and falls risk assessment• Drug treatment to reduce risk of further fracture • Help to prevent further falls

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Summary 1

• Osteoporosis is a common condition that can lead to painful and disabling fractures

• Those at risk need appropriate assessment of their bone fragility

• A healthy lifestyle can help to build and maintain strong bones and prevent fractures

85

Summary 2

• Drug treatments to reduce the risk of fractures are available for those at the highest risk

• Help and pain management after fractures are essential so that people regain a good quality of life and further fractures are prevented

osteoporotic back pain

Health & Medicine