Post on 14-Jul-2015
UPDATES IN DIAGNOSIS & UPDATES IN DIAGNOSIS & TREATMENT OF OSTEOPOROSISTREATMENT OF OSTEOPOROSIS
Dr Shahjada SelimDr Shahjada Selim
Assistant ProfessorAssistant Professor
Department of Endocrinology & MetabolismDepartment of Endocrinology & Metabolism
Bangabandhu Sheikh Mujib Medical UniversityBangabandhu Sheikh Mujib Medical University
Dhaka, BangladeeshDhaka, Bangladeesh
OsteoporosisOsteoporosis
Osteoporosis is defined as a low bone mass Osteoporosis is defined as a low bone mass with bone mass with bone arcitechturoul with bone mass with bone arcitechturoul deformity. deformity. NIH Consensus Development Conference, March 2000NIH Consensus Development Conference, March 2000
Normal Bone Osteoporotic Bone
Definition of a Fragility FractureDefinition of a Fragility Fracture
A fragility fracture is one that results A fragility fracture is one that results from mechanical forces that would from mechanical forces that would not ordinarily cause fracture in a not ordinarily cause fracture in a healthy young adult.healthy young adult.
This is quantified as forces This is quantified as forces equivalent to a fall from a standing equivalent to a fall from a standing height or less.height or less.
OsteoporosisOsteoporosis8 million Osteoporotic Women and 2.5 million Osteoporotic Men in USA8 million Osteoporotic Women and 2.5 million Osteoporotic Men in USA
Expected to increase by about 40% by 2020 Expected to increase by about 40% by 2020 11
Estimated Estimated DirectDirect costs in 2001 = $ 11.6 - 17.1 billion annually costs in 2001 = $ 11.6 - 17.1 billion annually 11
Based on relative older Canadian population Based on relative older Canadian population 2 2 &&
Australian estimates of 7:1 ratio for Indirect to direct costs Australian estimates of 7:1 ratio for Indirect to direct costs 33
⇒⇒ $6 - $40 million every single day in Canada$6 - $40 million every single day in Canada
Mortality increased 2-3 fold in women and womenMortality increased 2-3 fold in women and women
after all types of Osteoporotic fractures after all types of Osteoporotic fractures 44
1 Surgeon-Generals Report2 Canadian and US census data
3 Access Economics, 4 Center 1999
Prevalence of VCF’sPrevalence of VCF’s
Lifetime prevalence in Caucasians:Lifetime prevalence in Caucasians:15% in women15% in women
5-9% in men5-9% in men
Higher than risk of breast cancerHigher than risk of breast cancer
Osteoporotic fractures, Cardiovascular events & Osteoporotic fractures, Cardiovascular events & Breast cancerBreast cancer
in osteoporotic postmenopausal women in osteoporotic postmenopausal women
Any fracture
Spine #
Clinical S
pine #
Hip fracture
CVS event
Breast
Cancer
No prior spine fracture (938)
Prior spine fracture (1627)0
20
40
60
80
100
120
from Silverman et al, 2004J Am Geriatr Soc 52:1543-8
Eventsper 1000 women-yr
MORE studyplacebo armover 3 years
SITESITE INCREASE IN INCREASE IN MORTALITY RISKMORTALITY RISK
VertebraeVertebrae 8.68.6
HipHip 6.76.7
Any Clinical FractureAny Clinical Fracture 2.22.2
Fracture and Mortality Risk
Each year, one in three Ontarians over the ageof 65 will take a serious tumble that may landthem in hospital with a broken hip. One in threeof those who do break their hip will die withina year. Two thirds will experience dementia-likesymptoms. Most will never see home again.
Osteoporosis-associated Osteoporosis-associated MortalityMortality
Age-standardised mortality riskAge-standardised mortality riskincreased 2-3 foldincreased 2-3 fold
after all types of osteoporotic fractureafter all types of osteoporotic fracture
WomenWomen Men Men
Proximal femur Proximal femur 2.22.2 3.2 3.2
VertebralVertebral 1.71.7 2.4 2.4
Other majorOther major 1.91.9 2.2 2.2
Center et al, Lancet 1999
““THE CARE GAP”THE CARE GAP”IN OSTEOPOROSISIN OSTEOPOROSIS
Despite the introduction of methods to Despite the introduction of methods to identify those with osteoporosis and identify those with osteoporosis and despite effective treatment, a large despite effective treatment, a large ‘care gap’ continues to exist for these ‘care gap’ continues to exist for these patients. patients.
Recommendations for Bone Recommendations for Bone Mineral Density Reporting in Mineral Density Reporting in
CanadaCanada..
Siminoski K, Leslie WD, Brown JP, Frame H, Hodsman A, Josse RG, Khan A, Lentle BC, Levesque J, Lyons DJ, Tarulli G
Can Assoc Radiol J 2005; 56: 178-188
2002 Definitions: BMD Results2002 Definitions: BMD Results
1. Kanis JA, et al. J Bone Miner Res 1994;9:1137-1141.2. WHO, Geneva 1994.
StatusStatus 1, 21, 2 T-scoreT-score
NormalNormal +2.5 to +2.5 to −−1.0, inclusive1.0, inclusive
OsteopeniaOsteopenia Between Between −−1.0 and 1.0 and −−2.52.5
OsteoporosisOsteoporosis ≤−≤−2.52.5
Severe osteoporosisSevere osteoporosis ≤−≤−2.5 + fragility fracture2.5 + fragility fracture
ABOUTABOUTT-SCORES?T-SCORES?
Advantages
Unitless
Basis for the majority of osteoporosis guidelines
Simplicity
Disadvantages
Depends on site measured
Depends on technology
Depends on reference database—population mean
and standard deviation
Only includes BMD information and not additional
risk factors
Adapted from Faulkner K. Osteoporos Int 2005;16(4):347-52.
Fracture RiskFracture Riskvs. BMDvs. BMDAt Different AgesAt Different Ages
Fracture RiskFracture Riskvs. BMDvs. BMDAt Different AgesAt Different Ages
BMD PREDICTS FRACTURESBMD PREDICTS FRACTURES
Hui et al. J Clin Invest 1988; 81:1804-9
AGEAGE T-Score T-Score
= -1.0= -1.0T-ScoreT-Score
= -2.5= -2.5
5050 6 %6 % 11 %11 %
6060 8 %8 % 16 %16 %
7070 12 %12 % 23 %23 %
8080 13 %13 % 26 %26 %
Risk of Fractures Over 10 Years in WomenRisk of Fractures Over 10 Years in Women
Proposed ChangeProposed Change
Previous OSC guidelines advised intervention Previous OSC guidelines advised intervention based on WHO category as a marker of relative based on WHO category as a marker of relative fracture risk.fracture risk.
Now propose that an Now propose that an individual’s 10-year individual’s 10-year absolute fracture riskabsolute fracture risk, rather than BMD alone, , rather than BMD alone, be used for fracture risk categorizationbe used for fracture risk categorization
5-STEPS IN5-STEPS IN TREATING OSTEOPOROSISTREATING OSTEOPOROSIS
STEPS 1 and 2STEPS 1 and 2
Begin with the table appropriate for Begin with the table appropriate for the patient’s sex the patient’s sex Identify the row that is closest to Identify the row that is closest to the patient's agethe patient's age
CATEGORIZATION BASED ON 10-YEAR CATEGORIZATION BASED ON 10-YEAR FRACTURE RISKFRACTURE RISK
Absolute fracture risk in 10 years:Absolute fracture risk in 10 years:
low: low: <10%<10%
moderate: moderate: 10-20%10-20%
high: high: >20%>20%
USING LOWEST T-SCORE TO FIND 10-YEAR USING LOWEST T-SCORE TO FIND 10-YEAR FRACTURE RISK - WOMENFRACTURE RISK - WOMEN
WOMEN
-4.5
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
50 55 60 65 70 75 80 85
AGE (years)
LO
WE
ST
T-S
co
re
Moderate RiskModerate Risk
High RiskHigh Risk
Low Risk
5-STEPS IN5-STEPS IN TREATING OSTEOPOROSISTREATING OSTEOPOROSIS
STEP 3STEP 3
Determine the preliminary fracture risk Determine the preliminary fracture risk category by using the lowest T-score category by using the lowest T-score from the recommended skeletal sitesfrom the recommended skeletal sites
5-STEPS IN5-STEPS IN TREATING OSTEOPOROSISTREATING OSTEOPOROSIS
STEP 4STEP 4
Evaluate clinical factors that may move Evaluate clinical factors that may move the patient into an even higher fracture the patient into an even higher fracture risk categoryrisk category
USING LOWEST T-SCORE TO FIND 10-YEAR USING LOWEST T-SCORE TO FIND 10-YEAR FRACTURE RISK - MENFRACTURE RISK - MEN
MEN
-4.5
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
50 55 60 65 70 75 80 85
AGE (years)
LOW
EST
T-Sc
ore
Low RiskLow Risk
High RiskHigh Risk
Moderate RiskModerate Risk
Additional Clinical FactorsAdditional Clinical Factors
Certain clinical factors increase fracture Certain clinical factors increase fracture risk independent of BMD.risk independent of BMD.
The most important are:The most important are:– Fragility fractures after age 40 (especially Fragility fractures after age 40 (especially
vertebral compression fractures)vertebral compression fractures)– Systemic glucocorticoid therapy >3 months Systemic glucocorticoid therapy >3 months
duration.duration.
Additional Risk FactorsAdditional Risk Factors
Each factor effectively increases risk Each factor effectively increases risk categorization to the next level:categorization to the next level:– from low risk to moderate risk, orfrom low risk to moderate risk, or– from moderate risk to high riskfrom moderate risk to high risk
When both factors are present the When both factors are present the patient should be considered at high patient should be considered at high risk regardless of the BMD result.risk regardless of the BMD result.
5-STEPS IN5-STEPS IN TREATING OSTEOPOROSISTREATING OSTEOPOROSIS
STEP 5STEP 5
Determine the individual’s final Determine the individual’s final absolute fracture risk category.absolute fracture risk category.
Woman – age 52Woman – age 52
- t is -2.6- t is -2.6
Fracture Risk Category?Fracture Risk Category?
CASE EXAMPLECASE EXAMPLE
High RiskHigh Risk
Moderate RiskModerate Risk
Low RiskLow Risk
WOMEN
-4.5
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
50 55 60 65 70 75 80 85
AGE (years)
LO
WE
ST
T-S
core
CASE EXAMPLECASE EXAMPLE
Low RiskModerate Risk
High Risk
AGE LOW MODERATE HIGH<10% 10 to 20% >20%
50 >-2.3 -2.2 to -3.9 <-3.955 >-1.9 1.9 to -3.4 <-3.460 >-1.4 -1.4 to -3.0 <-3.065 >-1.0 -1.0 to -2.6 <-2.670 >-0.8 -0.8 to -2.2 <-2.275 >-0.7 -0.7 to -2.1 <-2.180 >-0.6 -0.6 to -2.0 <-2.085 >-0.7 -0.7 to -2.2 <-2.2
10-YEAR RISK
WOMEN
CASE EXAMPLECASE EXAMPLE
-2.2- -3.9
Fracture Risk CategoryFracture Risk Category
High RiskHigh Risk
Moderate RiskModerate Risk
If Fragility Fracture HistoryIf Fragility Fracture History
CASE EXAMPLECASE EXAMPLE
70 year-old man70 year-old man
CASE EXAMPLE CASE EXAMPLE
Lowest T-score –2.7 in total hipLowest T-score –2.7 in total hip
BMD done because of strong family BMD done because of strong family history of osteoporosis history of osteoporosis (mother fractured hip, sister (mother fractured hip, sister
has OP)has OP)
USING LOWEST T-SCORE TO FIND 10-YEAR USING LOWEST T-SCORE TO FIND 10-YEAR FRACTURE RISK - MENFRACTURE RISK - MEN
MEN
-4.5
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
50 55 60 65 70 75 80 85
AGE (years)
LOW
EST
T-Sc
ore
Low RiskLow Risk
High RiskHigh Risk
Moderate RiskModerate RiskX
OTHER ISSUES FOR THIS 70 OTHER ISSUES FOR THIS 70 YEAR OLD MALEYEAR OLD MALE
Chest x-ray – mild loss of vertebral height Chest x-ray – mild loss of vertebral height at T4, T5at T4, T5
What if he had had polymyalgia What if he had had polymyalgia rheumatica at age 69 and was on rheumatica at age 69 and was on prednisone 10 mg./day?prednisone 10 mg./day?
Fracture Risk CategoryFracture Risk Category
Moderate RiskModerate Risk
If Fragility Fracture History, If Fragility Fracture History, Corticosteroid useCorticosteroid use
High RiskHigh Risk
CASE EXAMPLECASE EXAMPLE
EndorsementsEndorsements
Canadian Association of Nuclear MedicineCanadian Association of Nuclear Medicine
Canadian Association of RadiologistsCanadian Association of Radiologists
Canadian Rheumatology AssociationCanadian Rheumatology Association
International Society of Clinical DensitometryInternational Society of Clinical Densitometry
Society of Obstetricians and Gynecologists of CanadaSociety of Obstetricians and Gynecologists of Canada
Canadian Society of Endocrinology and Metabolism Canadian Society of Endocrinology and Metabolism
Canadian Orthopedic AssociationCanadian Orthopedic Association
College of Family Physicians of CanadaCollege of Family Physicians of Canada
Osteoporosis Prevention and Osteoporosis Prevention and TreatmentTreatment
Age
Hormonal Replacement
Bisphosphonates Strontium
SERM
20 40 60 80
Vitamin D
PTH
Life Style
Treatmentchoice
** with prev vert fracture(s) with prev vert fracture(s) **** without prev vert fractures without prev vert fractures ****** with or without prev verfractures with or without prev verfractures
Antifracture efficacy of antiosteoporotic agents
0.6 1.00.2
Incident nonvertebral fractures Relative risk
RLX 60, 120(MORE)***
CT 200 (PROOF)*
Teriparatide 20µg*
ALN 5/10 (FIT1)*
ALN 5/10 (FIT2)**
RIS 5 (VERT-NA)*
RIS 5 (VERT-MN)*
RIS 2.5/5 (Hip Study)***RIS 2.5/5 (Hip Study)***
Incident vertebral fractures Relative risk
0.60.6 1.01.00.20.2
RLX 60 (MORE)*
RLX 60 (MORE)**
CT 200 (PROOF)*
Teriparatide 20µg*
ALN 5/10 (FIT1)*
ALN 5/10 (FIT2)**
RIS 5 (VERT-NA)*
RIS 5 (VERT-MN)*
Strontium ranelate(SOTI)*
Strontium ranelate(SOTI +TROPOS)**
Strontium ranelate(TROPOS)***
Strontium ranelate(SOTI)*
Updated from Delmas, Lancet 2002
RR ± 95% CI
Medications Available for Medications Available for Post-Menopausal OsteoporosisPost-Menopausal Osteoporosis
ActonelActonel®® (risedronate sodium tablets) (1/day;1/wk; 1/mo) (risedronate sodium tablets) (1/day;1/wk; 1/mo)
Didrocal® (etidronate sodium tablets)Didrocal® (etidronate sodium tablets)
FosamaxFosamax®® (alendronate sodium tablets) 1day/1/wk; Fosovance) (alendronate sodium tablets) 1day/1/wk; Fosovance)
Aclasta Aclasta ® ® (zolendronate IV) (zolendronate IV)
Estrogen (some use)Estrogen (some use)
EvistaEvista®® (raloxifene HCl) (raloxifene HCl)
MiacalcinMiacalcin®® (calcitonin salmon) Nasal Spray (calcitonin salmon) Nasal Spray
Forteo (Teriparatide) (sc)Forteo (Teriparatide) (sc)
Consult with your physician to determine what medication may Consult with your physician to determine what medication may be best for yoube best for you
Bisphosphonates — Cyclical Bisphosphonates — Cyclical EtidronateEtidronate
pp=NS=NS
00
1010
2020
3030
4040
5050
1818
Etidronate (n = 20)Etidronate (n = 20)
4343
Placebo (n = 20)Placebo (n = 20)
Lum
bar
spin
e fr
actu
re r
ate
Lum
bar
spin
e fr
actu
re r
ate
(fra
ctur
es/1
00 p
atie
nt-y
ears
(fra
ctur
es/1
00 p
atie
nt-y
ears
))
Storm T. Storm T. N Engl J MedN Engl J Med 1990; 1990;322322:1265.:1265.
• 3-year RCT, 66 subjects3-year RCT, 66 subjects• High risk subgroup: reduction in fracture rate with etidronate, High risk subgroup: reduction in fracture rate with etidronate, pp = 0.023 = 0.023 • No statistically significant effect at nonvertebral sitesNo statistically significant effect at nonvertebral sites
Cumulative Hip Fracture Cumulative Hip Fracture IncidenceIncidence
Baseline Month 6 Month 12
% o
f c
oh
ort
wit
h a
hip
fra
ctu
re
0.00
0.10
0.20
0.30
0.40
0.50
0.58
alendronate
risedronate
Silverman SL. Osteoporos Int 2007 Jan;18(1):25-34. Epub 2006 Nov 15.
↓ 43%*Adjusted Relative Rate Reduction at Month 12
p = 0.0195% CI: 13% - 63%
↓ 46%*Adjusted Relative Rate Reduction at Month 6
p = 0.0295% CI: 9% - 68%
80 fracturesn= 21,615
29 fracturesn = 12,215
HIP FRACTURESHIP FRACTURES MORBIDITY AND MORTALITY MORBIDITY AND MORTALITY
“One-third of all hip fractures occur in men and are associated with as much illness and increased risk of death as those that occur in women .”
“The average 50-year-old Caucasian man has a 13 per cent chance of having a fracture related to osteoporosis sometime in his remaining lifetime. A 60-year-old Caucasian man has a 29 per cent chance.”
Dr. John Schousboe, Minneapolis 2007
Male Osteoporosis: Morbidity and Male Osteoporosis: Morbidity and MortalityMortality
As compared to women, while lifetime As compared to women, while lifetime fracture risk may be less,fracture risk may be less,– Men have higher rates of morbidity and Men have higher rates of morbidity and
mortality due to fracturesmortality due to fractures– Men are twice as likely to die in hospital after Men are twice as likely to die in hospital after
a hip fracturea hip fracture– Men have a higher mortality rate than women Men have a higher mortality rate than women
one year after a hip fractureone year after a hip fracture
Cooper C, et al. Osteoporos Int 1992;2:285-9; Singer BR, et al. J Bone Joint Surg Br 1998;80:243-8; Center JR, et al. The Lancet 1999;353:878-82; Forsen L, et al. Osteoporos Int 1999;10:73-8; Johnell O., et al. Calcif Tissue Int 2001;69:182-4; Amin S. Curr Osteoporos Rep 2003;1:71-7; Campion JM, et al. Am Fam Phys 2003;67:1521-6.
GLUCOCORTICOIDS and BONEGLUCOCORTICOIDS and BONE
Have a reflex! SGC > 3 mo > 7.5 mg./day Have a reflex! SGC > 3 mo > 7.5 mg./day
-Ca, vitamin D, bisphosphonate-Ca, vitamin D, bisphosphonate
Bone density evaluation?Bone density evaluation?
Back injuries.Back injuries. If you think that golf is for wimps, consider If you think that golf is for wimps, consider this: A this: A golf swinggolf swing puts a higher compressive load on the puts a higher compressive load on the low back (low back (8 times body weight8 times body weight) than ) than runningrunning ( (33 timestimes) or ) or even even rowingrowing ( (77 timestimes). That’s why a single swing can ). That’s why a single swing can produce a herniated disc or even a produce a herniated disc or even a compressioncompression fracturefracture of one of the vertebral bodies. Although these injuries of one of the vertebral bodies. Although these injuries are extremely painful and can be quite serious, they are are extremely painful and can be quite serious, they are rare. Muscle strains, however, are quite common rare. Muscle strains, however, are quite common because of the twisting that is required for a good swing. because of the twisting that is required for a good swing. The “modern” swing, with its inverted-C follow-through, The “modern” swing, with its inverted-C follow-through, may make for longer drives than the “classic” swing but it may make for longer drives than the “classic” swing but it also produces more torque — and more injuries (also produces more torque — and more injuries (seesee Golf injuries Golf injuries aboveabove). ).
Harvard Men’s Health Watch Aug 2004
SUMMARYSUMMARYREDUCING THE ‘CARE GAP’REDUCING THE ‘CARE GAP’
Assess bone health in woman >50 and in Assess bone health in woman >50 and in men > 60.men > 60.
Evaluate risk factors; evaluate BMDEvaluate risk factors; evaluate BMD
Consider preventative approach to Consider preventative approach to reduction of fracture risk (the way you reduction of fracture risk (the way you think of hypertension and MI and stroke)think of hypertension and MI and stroke)
Treat and monitor Treat and monitor