Advances in Diagnosis and Treatment of Osteoporosis

Published on July 2016 | Categories: Documents | Downloads: 29 | Comments: 0 | Views: 292
of x
Download PDF   Embed   Report

osteoporosis

Comments

Content

ADVANCES IN DIAGNOSIS & TREATMENT OF OSTEOPOROSIS
Jerry Tenenbaum MD FRCPC Professor of Medicine:University of Toronto Mount Sinai Hospital

DISCLOSURES
SPEAKER ON OCCASION FOR 1. P&G 2. Pfizer 3. Merck 4. Novartis

GOAL
Review advances in the diagnosis and treatment of osteoporosis

OBJECTIVES
1. Show the impact of osteoporosis on the

health of the elderly
2. Advise on screening and diagnosis of

osteoporosis
3. Outline evidence-based treatment

Osteoporosis
Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture.
NIH Consensus Development Conference, March 2000

Normal Bone

Osteoporotic Bone

Vertebral Fracture Cascade

THE HUMAN COST Downward Spiral

Definition of a Fragility Fracture
A fragility fracture is one that results from mechanical forces that would not ordinarily cause fracture in a healthy young adult.
This is quantified as forces equivalent to a fall from a standing height or less.

Osteoporosis
8 million Osteoporotic Women and 2.5 million Osteoporotic Men in USA
Expected to increase by about 40% by 2020 1 Estimated Direct costs in 2001 = $ 11.6 - 17.1 billion annually 1

Based on relative older Canadian population 2 &
Australian estimates of 7:1 ratio for Indirect to direct costs 3  $6 - $40 million every single day in Canada

Mortality increased 2-3 fold in women and women
after all types of Osteoporotic fractures 4

Report and US census data 3 Access Economics, 4 Center 1999
2 Canadian

1 Surgeon-Generals

Prevalence of VCF‘s
Lifetime prevalence in Caucasians:
15% in women 5-9% in men

Higher than risk of breast cancer

Osteoporotic fractures, Cardiovascular events & Breast cancer in osteoporotic postmenopausal women
120

Events per 1000 women-yr

100 80 60 40 20 0

MORE study placebo arm over 3 years

Prior spine fracture (1627) No prior spine fracture (938) from Silverman et al, 2004 J Am Geriatr Soc 52:1543-8

Fracture and Mortality Risk
SITE
Vertebrae Hip Any Clinical Fracture

INCREASE IN MORTALITY RISK 8.6
6.7 2.2

Each year, one in three Ontarians over the age of 65 will take a serious tumble that may land them in hospital with a broken hip. One in three of those who do break their hip will die within a year. Two thirds will experience dementia-like symptoms. Most will never see home again.

Osteoporosis-associated Mortality
Age-standardised mortality risk increased 2-3 fold after all types of osteoporotic fracture Women 2.2 1.7 1.9 Men 3.2 2.4 2.2

Proximal femur
Vertebral Other major

Center et al, Lancet 1999

―THE CARE GAP‖ IN OSTEOPOROSIS

Despite the introduction of methods to identify those with osteoporosis and despite effective treatment, a large ‗care gap‘ continues to exist for these patients.

THE TIP OF THE ICEBERG

ASSESSMENT

MANAGEMENT

Recommendations for Bone Mineral Density Reporting in Canada.
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 Results
Status 1, 2 Normal Osteopenia Osteoporosis Severe osteoporosis T-score +2.5 to −1.0, inclusive Between −1.0 and −2.5 ≤−2.5 ≤−2.5 + fragility fracture

1. Kanis JA, et al. J Bone Miner Res 1994;9:1137-1141. 2. WHO, Geneva 1994.

ABOUT 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.

BMD PREDICTS FRACTURES
Fracture Risk vs. BMD At Different Ages

Hui et al. J Clin Invest 1988; 81:1804-9

Risk of Fractures Over 10 Years in Women AGE T-Score = -1.0 T-Score = -2.5

50 60
70

6% 8%
12 %

11 % 16 %
23 %

80

13 %

26 %

Proposed Change
Previous OSC guidelines advised intervention based on WHO category as a marker of relative fracture risk.
Now propose that an individual‘s 10-year absolute fracture risk, rather than BMD alone, be used for fracture risk categorization

5-STEPS IN TREATING OSTEOPOROSIS STEPS 1 and 2
Begin with the table appropriate for the patient‘s sex Identify the row that is closest to the patient's age

CATEGORIZATION BASED ON 10-YEAR FRACTURE RISK

Absolute fracture risk in 10 years: low: <10% moderate: 10-20% high: >20%

USING LOWEST T-SCORE TO FIND 10-YEAR FRACTURE RISK - WOMEN

WOMEN
0.0 -0.5

Low Risk

LOWEST T-Score

-1.0 -1.5 -2.0 -2.5 -3.0 -3.5 -4.0 -4.5 50 55 60 65 70 75 80 85

Moderate Risk

High Risk

AGE (years)

5-STEPS IN TREATING OSTEOPOROSIS STEP 3
Determine the preliminary fracture risk category by using the lowest T-score from the recommended skeletal sites

5-STEPS IN TREATING OSTEOPOROSIS STEP 4
Evaluate clinical factors that may move the patient into an even higher fracture risk category

USING LOWEST T-SCORE TO FIND 10-YEAR FRACTURE RISK - MEN
MEN
0.0
LOWEST T-Score

-0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 -4.0 -4.5 50

Low Risk Moderate Risk

High Risk
55 60 65 70 75 80 85

AGE (years)

Additional Clinical Factors
Certain clinical factors increase fracture risk independent of BMD. The most important are:
– Fragility fractures after age 40 (especially vertebral compression fractures) – Systemic glucocorticoid therapy >3 months duration.

Additional Risk Factors
Each factor effectively increases risk categorization to the next level:
– from low risk to moderate risk, or – from moderate risk to high risk

When both factors are present the patient should be considered at high risk regardless of the BMD result.

5-STEPS IN TREATING OSTEOPOROSIS STEP 5
Determine the individual‘s final absolute fracture risk category.

CASE EXAMPLE
Woman – age 52 - t is -2.6 Fracture Risk Category?

CASE EXAMPLE
WOMEN
0.0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 -4.0 -4.5 50 55 60 65 70 75 80 85

Low Risk

LOWEST T-Score

Low Risk

Moderate Risk

Moderate Risk
High Risk

High Risk
AGE (years)

CASE EXAMPLE
WOMEN
AGE
50 55 60 65 70 75 80 85

LOW <10%
>-2.3 >-1.9 >-1.4 >-1.0 >-0.8 >-0.7 >-0.6 >-0.7

10-YEAR RISK MODERATE 10 to 20%
-2.2-2.2 to -3.9 -3.9 1.9 to -3.4 -1.4 to -3.0 -1.0 to -2.6 -0.8 to -2.2 -0.7 to -2.1 -0.6 to -2.0 -0.7 to -2.2

HIGH >20%
<-3.9 <-3.4 <-3.0 <-2.6 <-2.2 <-2.1 <-2.0 <-2.2

CASE EXAMPLE
Fracture Risk Category Moderate Risk

CASE EXAMPLE
Fracture Risk Category Moderate Risk If Fragility Fracture History High Risk

CASE EXAMPLE

70 year-old man BMD done because of strong family history of osteoporosis (mother fractured hip, sister has OP) Lowest T-score –2.7 in total hip

USING LOWEST T-SCORE TO FIND 10-YEAR FRACTURE RISK - MEN
MEN
0.0
LOWEST T-Score

-0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 -4.0 -4.5 50

Low Risk
X

Moderate Risk

High Risk
55 60 65 70 75 80 85

AGE (years)

CASE EXAMPLE
Fracture Risk Category

Moderate Risk

OTHER ISSUES FOR THIS 70 YEAR OLD MALE
Chest x-ray – mild loss of vertebral height at T4, T5 What if he had had polymyalgia rheumatica at age 69 and was on prednisone 10 mg./day?

CASE EXAMPLE
Fracture Risk Category Moderate Risk If Fragility Fracture History, Corticosteroid use High Risk

Endorsements
Canadian Association of Nuclear Medicine Canadian Association of Radiologists Canadian Rheumatology Association International Society of Clinical Densitometry Society of Obstetricians and Gynecologists of Canada Canadian Society of Endocrinology and Metabolism

Canadian Orthopedic Association College of Family Physicians of Canada

Osteoporosis Prevention and Treatment
Treatment choice Hormonal Replacement SERM Bisphosphonates
Strontium

PTH
Vitamin D Life Style

20

40

60

80

Age

Antifracture efficacy of antiosteoporotic agents
Incident vertebral fractures
Relative risk
RLX 60 (MORE)* RLX 60 (MORE)** ALN 5/10 (FIT1)*

Incident nonvertebral fractures
Relative risk

RR ± 95% CI
RLX 60, 120 (MORE)*** ALN 5/10 (FIT1)*

ALN 5/10 (FIT2)** RIS 5 (VERT-NA)*
RIS 5 (VERT-MN)*

ALN 5/10 (FIT2)**
RIS 5 (VERT-NA)* RIS 5 (VERT-MN)* RIS 2.5/5 (Hip Study)***

CT 200 (PROOF)* Teriparatide 20µg* Strontium ranelate (SOTI)* Strontium ranelate (SOTI +TROPOS)** 0.2 0.6 1.0

CT 200 (PROOF)* Teriparatide 20µg* Strontium ranelate (SOTI)* Strontium ranelate (TROPOS)*** 0.2 0.6 1.0

* with prev vert fracture(s) ** without prev vert fractures

*** with or without prev verfractures
Updated from Delmas, Lancet 2002

Medications Available for Post-Menopausal Osteoporosis
Actonel® (risedronate sodium tablets) (1/day;1/wk; 1/mo)
Didrocal® (etidronate sodium tablets) Fosamax® (alendronate sodium tablets) 1day/1/wk; Fosovance) Aclasta ® (zolendronate IV) Estrogen (some use) Evista® (raloxifene HCl) Miacalcin® (calcitonin salmon) Nasal Spray Forteo (Teriparatide) (sc) Consult with your physician to determine what medication may be best for you

Bisphosphonates — Cyclical Etidronate
Lumbar spine fracture rate (fractures/100 patient-years)
50 43 40

30
20 10 0 18

Placebo (n = 20)
• • •

Etidronate (n = 20)

3-year RCT, 66 subjects High risk subgroup: reduction in fracture rate with etidronate, p = 0.023 No statistically significant effect at nonvertebral sites

p=NS

Storm T. N Engl J Med 1990;322:1265.

Cumulative Hip Fracture Incidence
0.58

alendronate
% of cohort with a hip fracture
0.50

80 fractures n= 21,615

0.40

29 fractures n = 12,215

0.30

risedronate
↓ 46%*
Adjusted Relative Rate Reduction at Month 6 p = 0.02 95% CI: 9% - 68%
Month 6

0.20

↓ 43%*
Adjusted Relative Rate Reduction at Month 12 p = 0.01 95% CI: 13% - 63%
Month 12

0.10

0.00 Baseline

Silverman SL. Osteoporos Int 2007 Jan;18(1):25-34. Epub 2006 Nov 15.

Osteoporosis in Men
Has Its Time Come?

HEADLINES 7.8.07

HIP FRACTURES 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 Mortality
As compared to women, while lifetime fracture risk may be less,
– Men have higher rates of morbidity and mortality due to fractures – Men are twice as likely to die in hospital after a hip fracture – Men have a higher mortality rate than women one 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

GLUCOCORTICOIDS and BONE
Have a reflex! SGC > 3 mo > 7.5 mg./day -Ca, vitamin D, bisphosphonate

Bone density evaluation?

Back injuries. If you think that golf is for wimps, consider this: A golf swing puts a higher compressive load on the low back (8 times body weight) than running (3 times) or even rowing (7 times). That‘s why a single swing can produce a herniated disc or even a compression fracture of one of the vertebral bodies. Although these injuries are extremely painful and can be quite serious, they are rare. Muscle strains, however, are quite common because of the twisting that is required for a good swing. The ―modern‖ swing, with its inverted-C follow-through, may make for longer drives than the ―classic‖ swing but it also produces more torque — and more injuries (see Golf injuries above).

Harvard Men‘s Health Watch Aug 2004

SUMMARY REDUCING THE ‗CARE GAP‘
Assess bone health in woman >50 and in men > 60. Evaluate risk factors; evaluate BMD Consider preventative approach to reduction of fracture risk (the way you think of hypertension and MI and stroke) Treat and monitor

Sponsor Documents

Or use your account on DocShare.tips

Hide

Forgot your password?

Or register your new account on DocShare.tips

Hide

Lost your password? Please enter your email address. You will receive a link to create a new password.

Back to log-in

Close