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ADVANCES IN DIAGNOSIS _ TREATMENT OF OSTEOPOROSIS

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					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




                                                         1 Surgeon-Generals   Report
                                                    2 Canadian and US census data
                                                  3 Access Economics, 4 Center 1999
   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    100                               MORE study
per 1000                                     placebo arm
women-yr                                     over 3 years
           80

           60

           40

           20

            0
                                     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             INCREASE IN
                        MORTALITY RISK
Vertebrae                    8.6

Hip                          6.7

Any Clinical Fracture        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                Men
Proximal femur               2.2                  3.2

Vertebral                      1.7                2.4

Other major                    1.9                2.2




                                 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




                                      MANAGEMENT
ASSESSMENT
 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                  T-score
Normal                       +2.5 to −1.0, inclusive
Osteopenia                   Between −1.0 and −2.5
Osteoporosis                 ≤−2.5
Severe osteoporosis          ≤−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                            Disadvantages
        Unitless                     Depends on site measured
Basis for the majority of               Depends on technology
osteoporosis guidelines
                                        Depends on reference
       Simplicity                    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      T-Score
                 = -1.0       = -2.5
     50            6%          11 %

     60            8%          16 %

     70          12 %          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



     Low Risk

                Moderate Risk


                           High Risk
        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




      Low Risk

                     Moderate Risk


                           High Risk
  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


Low Risk
  Low Risk     Moderate Risk

             Moderate Risk

                         High Risk
                    High Risk
CASE EXAMPLE




       -2.2- -3.9
        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




      Low Risk

                     Moderate Risk
                    X


                           High Risk
        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
                     Hormonal Replacement
Treatment                 SERM
  choice                         Bisphosphonates
                                    Strontium
                                            PTH

                                            Vitamin D
        Life Style


      20       40      60      80     Age
 Antifracture efficacy of antiosteoporotic agents
             Incident vertebral fractures                               Incident nonvertebral fractures
                            Relative risk             RR ± 95% CI                              Relative risk

RLX 60 (MORE)*                                                RLX 60, 120
RLX 60 (MORE)**                                               (MORE)***

ALN 5/10 (FIT1)*                                              ALN 5/10 (FIT1)*
ALN 5/10 (FIT2)**                                             ALN 5/10 (FIT2)**

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

CT 200 (PROOF)*                                               CT 200 (PROOF)*

Teriparatide 20µg*                                            Teriparatide 20µg*

Strontium ranelate                                            Strontium ranelate
(SOTI)*                                                       (SOTI)*
Strontium ranelate                                            Strontium ranelate
(SOTI +TROPOS )**                                             (TROPOS)***

                            0.2       0.6       1.0                                      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
     (fractures/100 patient-years)




                                     50
      Lumbar spine fracture rate




                                                 43
                                     40

                                     30

                                     20                                          18

                                     10

                                     0
                                          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
                                                                                                  80 fractures
                                  0.58
                                                                                                  n= 21,615
                                                                  alendronate
                                  0.50
% of cohort with a hip fracture




                                  0.40
                                                                                                  29 fractures
                                                                                                  n = 12,215
                                  0.30
                                                                           risedronate

                                  0.20
                                                                      ↓ 46%*                       ↓ 43%*
                                                             Adjusted Relative Rate      Adjusted Relative Rate
                                  0.10                       Reduction at Month 6        Reduction at Month 12
                                                                    p = 0.02                    p = 0.01
                                                               95% CI: 9% - 68%            95% CI: 13% - 63%
                                  0.00
                                   Baseline                Month 6                         Month 12


                                              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

				
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