osteoporosis diagnosis and treatment

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How do we diagnose osteoporosis and making a treatment decission using BMD as a diagnostic tool. It also covers how do we assess clinical risk factors to make an intervention and to minimize fracture

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Osteoporosis ManagementOsteoporosis ManagementOsteoporosis ManagementOsteoporosis ManagementEfficacy and safety of bisphosphonates

Today’s talk :Today’s talk : Burden of the disease.Burden of the disease. Screening and treatment guidelines.Screening and treatment guidelines. Bisphosphonates.Bisphosphonates. Once yearly bisphoshonateOnce yearly bisphoshonate Controversial topics : Association of Controversial topics : Association of

bisphosphonates withbisphosphonates with ONJONJ Atypical femoral fracturesAtypical femoral fractures Atrial fibrillation. Atrial fibrillation. Esophageal cancer.Esophageal cancer.

Classic presentation

Burden of Disease Burden of Disease

2.52.5 million people in Indonesia have million people in Indonesia have

OsteoporosisOsteoporosis

88 million people in Indonesia have million people in Indonesia have

Osteopenia.Osteopenia.

Bone health and osteoporosis: Department of health & human Bone health and osteoporosis: Department of health & human

services 2004.services 2004.

Burden of DiseaseBurden of Disease

> 0,5 million> 0,5 million fractures/year due to either.fractures/year due to either.

75,00075,000 HIP fractures. HIP fractures.

150,000150,000 vertebral fractures. vertebral fractures.

35,00035,000 pelvic factures.pelvic factures.

Bone health and osteoporosis: Department of health & Bone health and osteoporosis: Department of health &

human services 2004.human services 2004.

Burden of Disease :Burden of Disease :

Hip fracturesHip fractures : : 50 %50 % Permanent impaired mobility. Permanent impaired mobility.

25 %25 % Loose skills to live Loose skills to live independently.independently.

Increased all cause mortality : first Increased all cause mortality : first 3 months3 months after hip fracture. after hip fracture.

1.2010 position statement of the North American Menopause Society. Menopause 2010.1.2010 position statement of the North American Menopause Society. Menopause 2010.

Annual incidenceAnnual incidence

Etiology of Bone loss in Etiology of Bone loss in OsteoporosisOsteoporosis

OSTEOCLAST - RESORPTIONOSTEOBLAST - FORMATION

Primary cause is estrogen deficiency+

Osteoporosis Osteoporosis

Risk factors Risk factors

Vertebral FracturesSemi-quantitative reading / visual scoring

Genant et al., J Bone Miner Res 1993, 8:137

Normal (Grade 0)

Wedge fracture Biconcave fracture Crush fracture

Mild fracture(Grade 1, ~20-25%)

Moderate fracture(Grade 2, ~25-40%)

Severe fracture(Grade 3, ~40%)

Who to screen Who to screen

Women > 65 years.Women > 65 years. Men > 70 years.Men > 70 years. Postmenopausal women /men >50 Postmenopausal women /men >50

years with clinical risk factors.years with clinical risk factors. H/o fracture at age > 50 years.H/o fracture at age > 50 years. Chronic steroid use.Chronic steroid use.

Direct measurement of BMD by DXA and as well as CT allows us to diagnose osteopenia

DXA

Fracture risk calculationFracture risk calculation

Who to treat ?Who to treat ?

Prior h/o hip/vertebral #Prior h/o hip/vertebral #

oror

T Score < -2.5T Score < -2.5

ororT Score -1 to -2.5 &10 yr risk (FRAX) :

HIP # > 3 % or major osteoporotic # > 20 %

T Score -1 to -2.5 &10 yr risk (FRAX) :

HIP # > 3 % or major osteoporotic # > 20 %

Postmenopausal women /men > 50 yrs

with

Recommendation for women and men > 50 Recommendation for women and men > 50 yo yo

• • Counsel on the risk of osteoporosis and related fractures.Counsel on the risk of osteoporosis and related fractures.

• • Advise on a diet rich in Advise on a diet rich in fruits and vegetables fruits and vegetables and that and that includes adequate amounts of total includes adequate amounts of total calcium intake calcium intake (1,000 (1,000 mg per day for men 50-70; 1,200 mg per day for women 51 mg per day for men 50-70; 1,200 mg per day for women 51 and older and men 71 and older).and older and men 71 and older).

• • Advise on Advise on vitamin Dvitamin D intake (800-1,000 IU per day), including intake (800-1,000 IU per day), including supplements if necessary for individuals age 50 and older.supplements if necessary for individuals age 50 and older.

• • Recommend regular Recommend regular weight-bearing and muscle-weight-bearing and muscle-strengthening strengthening exercise to improve agility, strength, posture exercise to improve agility, strength, posture and balance and reduce the risk of falls and fractures.and balance and reduce the risk of falls and fractures.

••Assess Assess risk factors risk factors for falls and offer for falls and offer appropriate modifications :appropriate modifications : home safety assessment, home safety assessment, balance training exercises, balance training exercises, correction of vitamin D insufficiency, correction of vitamin D insufficiency, avoidance of certain medications and avoidance of certain medications and bifocals use when appropriatebifocals use when appropriate

Calcium and vitamin Calcium and vitamin D D

Anti-resorptive

Anabolic

‘Dual action’

Bone marrow precursorsBone marrow precursors

OsteoblastsOsteoblastsOsteoclastOsteoclast

Lining cellsLining cells

Stimulators of Stimulators of Bone FormationBone Formation

FluorideFluoridePTH analogsPTH analogs

Sr Ranelate (?)Sr Ranelate (?)

Inhibitors ofInhibitors ofBone ResorptionBone Resorption Estrogen, SERMsEstrogen, SERMs

BisphosphonatesBisphosphonatesCalcitoninCalcitonin

Inhibitors ofRANKL

Cathepsin K

Therapeutic strategiesTherapeutic strategiesTherapeutic strategiesTherapeutic strategies

Treatments & Efficacy

Vertebral Fx Non-vertebral FxOther Fx Hip Fx

OralHRT Yes Yes YesEtidronate* YesAlendronate* Yes Yes YesRisedronate* Yes Yes YesIbandronate* Yes [Yes]Raloxifene* Yes Calcitriol* YesStrontium Ranelate* Yes Yes [Yes]

Vertebral Fx Non-vertebral FxOther Fx Hip Fx

Subcutaneous Teriparatide* Yes Yes 1-84 PTH* Yes Denosumab* Yes Yes Yes Intravenous Pamidronate Ibandronate*

Zoledronate* Yes Yes Yes Intranasal or Subcutaneous Calcitonin* Yes

Vertebral Fx Nonvertebral Fx

Other Fx Hip Fx

Alendronate* Yes Yes Yes

Risedronate* Yes Yes Yes

Zoledronic acid* Yes Yes Yes

PTH* Yes Yes ???

Strontium ranelate* Yes Yes ???

Denosumab* Yes Yes Yes

Appropriate use of appropriate treatments Appropriate use of appropriate treatments can halve the incidence of fractures can halve the incidence of fractures

* plus calcium + vitaminD

Mainstay of Mainstay of treatmenttreatment : :

BisphosphonatesBisphosphonatesApproval in US for osteoporosisApproval in US for osteoporosis Alendronate : 1995Alendronate : 1995 Risedronate : 2000Risedronate : 2000 Ibandronate : 2005Ibandronate : 2005 Zoledronate : 2007.Zoledronate : 2007.

Contraindications Contraindications

Duration of treatmentDuration of treatment

Cost factorCost factor

Alendronate: $4 - Alendronate: $4 - $40/month $40/month

Risedronate : $60 - Risedronate : $60 - $120/month $120/month

Ibandronate (oral): Ibandronate (oral): $90 - $130/month $90 - $130/month

IV Ibandronate : IV Ibandronate : $1300/year $1300/year

IV Zoledronate : IV Zoledronate : $1300/year$1300/year

Hot topics Hot topics

Osteonecrosis of jaw Osteonecrosis of jaw

ONJ ONJ Osteoporosis :Osteoporosis :

Reporting rate 1/100,000 - 1/250.000.Reporting rate 1/100,000 - 1/250.000. True incidence may be higher.True incidence may be higher.

Malignancy/skeletal metastasis : Malignancy/skeletal metastasis : Estd. Incidence: 1- 10 %Estd. Incidence: 1- 10 %

Risk factorsRisk factors

RecommendationsRecommendations

Atypical fractures Atypical fractures

Atypical fracturesAtypical fractures

? Long term over suppression of ? Long term over suppression of bone turnover.bone turnover.

Incidence : 1 in 10,000.Incidence : 1 in 10,000. Associated median treatment Associated median treatment

duration : 7 years.duration : 7 years. Causality : long term bp/ atypical # Causality : long term bp/ atypical #

unproven.unproven. Further large scale studies needed.Further large scale studies needed.

RecommendationsRecommendations

Educate physician/patient about Prodromal pain.Educate physician/patient about Prodromal pain. Evaluate with urgent X-Ray.Evaluate with urgent X-Ray. If negative, may consider MRI.If negative, may consider MRI. Stop BP’s if atypical fracture confirmed.Stop BP’s if atypical fracture confirmed.

Shane et al. ASBMR task report. J Bone Miner Res. 2010Shane et al. ASBMR task report. J Bone Miner Res. 2010

Atrial fibrillation Atrial fibrillation FDA recommends physicians FDA recommends physicians to not to not

alter their prescribing patternalter their prescribing patterns while it s while it continues to monitor post marketing continues to monitor post marketing reports of AF in such patients.reports of AF in such patients.

In v/o above and absence of definitive In v/o above and absence of definitive data : Benefits of treatment outweigh data : Benefits of treatment outweigh risks.risks.

Esophageal cancer Esophageal cancer 23 cases reported in last 2 23 cases reported in last 2

decades. (Wysowski et al)decades. (Wysowski et al) 31 cases from Europe/Japan.31 cases from Europe/Japan. Median time from use to Median time from use to

diagnosis : 1-2 yr.diagnosis : 1-2 yr. Time from exposure Time from exposure

inconsistent w/ causal inconsistent w/ causal relation.relation.

Further studies neededFurther studies needed..

Renal safetyRenal safety

Safe for creatinine clearance > 30 -35 Safe for creatinine clearance > 30 -35 mlml/min./min.

Lack of experience < 30 ml/min.Lack of experience < 30 ml/min. No data for use in ESRD.No data for use in ESRD. Exact bone disease unknown unless biopsy.Exact bone disease unknown unless biopsy. Expert opinion: half the dose could be used Expert opinion: half the dose could be used

for 3 years in ESRD once bone biopsy for 3 years in ESRD once bone biopsy confirms osteoporosis.confirms osteoporosis.

FractureBoneStrength

MaterialProperties

Remodeling

FallsShape & Architecture

Exercise & Lifestyle

Hormones

NutritionBone Mass

PosturalReflexes

Soft TissuePadding

Reproduced with permission from Heaney RP. Bone 33:457-465, 2003

Factors Leading to Osteoporotic Fracture: Role of Bone Remodeling

2004

HIP FRACTURE – Female Age 75 and overGive single oral dose 100,000 IU vitaminD @ as soon as feasible post hip fracture & start 1000mg

CaCO3+800IU vitaminD asap, (if on this already – continue)

Already on a BP(bisphosphonate)?

No

YesGood prognosis & eGFR 30 or over

Duration of treatment?Yes No

1. Patient or resident carer understand concepts of osteoporosis, fracture risk reduction & protocol for ingesting oral BPAND2. No contraindications to oral BPs [dysphagia / oesophageal stricture / achalasia /hypocalcaemia].

Yes

Oral ALN 70mg / wk

No

Patient suitable for IV BP& eGFR 35 or over

Yes No

Arrange IV zoledronic acid 5mg infusion (over at least 15min),

4-6/52 after hip fracture

Consider oral BP or, if at risk equivalent to that of fracture

plus T-score -2.4 or less, consider strontium ranelate.

Continue b.d. calcium + vitaminD

Continue b.d.oral calcium + vitaminD

More than 2yr 2yr or less

Optimal compliance with / adherence to BP & BP well tolerated

YesNo

Continue oral BPIF eGFR is 30 or moreOtherwise continue

b.d. calcium + vitaminD

GREATER GLASGOW & CLYDE PROTOCOL FOR FRACTURE SECONDARY PREVENTION AFTER HIP FRACTURE IN WOMEN AGE 75+

Zoledronic acid 5 mg IV once a year

Once Yearly Zoledronic Once Yearly Zoledronic Acid Reduces FracturesAcid Reduces Fractures

HORIZON Pivotal Fracture Trial Multi-national, multi-center, RCT 7,736 women age 65-89 with T-score <

-2.5 or fracture plus T-score < -1.5 Calcium 1000-1500 mg/day vit D (400-

1200 IU/day) Zoledronic acid IV infusion 5 mg

Black et al. NEJM 356:1809-1822, 2007

ZOLZOL reduces reduces hiphip fracture fracture

*Relative risk reduction (95% confidence interval) vs placeboBlack et al. NEJM 356:1809-1822, 2007

P = .0024

1

2

3

0

Placebo (n = 3861) ZOL 5 mg (n = 3875)

Cu

mu

lati

ve I

nci

den

ce (

%)

Time to First Hip Fracture (months)0 3 6 9 12 15 18 21 24 27 30 33 36

41%*(17%, 58%)

P < .0001

Cu

mu

lati

ve I

nci

den

ce (

%)

Time to First Clinical Vertebral Fracture (months)0 3 6 9 12 15 18 21 24 27 30 33 36

77%(63%, 86%)

Placebo (n = 3861) ZOL 5 mg (n = 3875)

1

2

3

0

ZOLZOL reduces reduces vertebral vertebral fxfx

*Relative risk reduction (95% confidence interval) vs placeboBlack et al. NEJM 356:1809-1822, 2007

P = .0002

Time to First Clinical Non-vertebral Fracture (months)

2

4

6

8

10

12

0 3 6 9 12 15 18 21 24 27 30 33 36

25%(13%, 36%)

Placebo (n = 3861) ZOL 5 mg (n = 3875)

0

Cu

mu

lati

ve I

nci

den

ce (

%)

ZOLZOL reduces reduces non-non-vertebralvertebral fx fx

*Relative risk reduction (95% confidence interval) vs placeboBlack et al. NEJM 356:1809-1822, 2007

Zoledronic Acid will Improve Zoledronic Acid will Improve Patient Patient Compliance as Compliance as Once-Yearly IV Therapy is Once-Yearly IV Therapy is

PreferredPreferred

Data from Lindsay R, et al. Poster presented at ECCEO6; March 15-18, 2006; Vienna, Austria.

16.4

18.9

Both Are EqualOnce-Yearly IV

Once-Weekly Pill

More convenient

More willing to take long term

Overall preference

N = 122

66.4

59.8

0 20 40 60 80 100

68.0

66.4

15.618.0

20.5

15.6

19.713.9

% of Patients

More satisfying

Take home points Take home points Osteoporosis : Osteoporosis : significant burden of diseasesignificant burden of disease.. Main stay treatment : Main stay treatment : bisphosphonatesbisphosphonates.. ? Duration of treatment : individualized.? Duration of treatment : individualized. Patient compliancePatient compliance

Patient educationPatient education once yearly IV BPonce yearly IV BP

More research needed to confirm association with More research needed to confirm association with ONJ, Sub trochanteric fracture.ONJ, Sub trochanteric fracture.

Benefits of treatment Benefits of treatment outweigh risks in osteoporosis.outweigh risks in osteoporosis.

Thank youThank you

Keep your bone Keep your bone healthyhealthy

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