Treatment of Osteoporosis

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					            Treatment of Osteoporosis
                   Drugs available today

                        Estrogen       Mechanism of Action
                     therapy (ERT)      They simply slow down
                                           bone resorption


             Receptor                … as a result,
               Raloxifene HCI        Maintain or increase bone mass
                                     Reduce fracture risk
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   Long-term prevention of bone loss by Estrogen

                                Treatment with Estrogen

                               Treatment with Estrogen

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                     Lindsay et al 1976 – Lancet I:1038-1040
   Estrogen Replacement Therapy
           in Osteoporosis

    • Decreases rate of bone loss after menopause

    • Maintains/increases BMD

    • Relieves postmenopausal symptoms

    • May prevent Alzheimer’s disease

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   Estrogen Replacement Therapy
           in Osteoporosis

     • Troublesome side effects, e.g., irregular bleeding, fluid
        retention, mastalgia, headache, mood swings (some from
        concomitant progestin)

     • Fracture risk data largely based on observational evidence

     •   Possible   increased risk of breast cancer with long-term use

     • Must be taken with progestin to avoid risk of endometrial
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Hormone Replacement Therapy

             … also a cure for
             heart disease ?

            … NOT as we thought
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            … the warning came

                      from the HERStudy
                       OSTEOPOROSIS       6
Estrogen’s effect on heart questioned
               A randomized Trial of
                  E2 + Progestin
                      on the
              20 Prevention of C H D
             Postmenopausal Women

            showed no overall effects after 4.1 years of Rx

                                            The Heart and
                                          Replacement Study
                                       JAMA Vol. 280 No. 7,
8/19/2010              OSTEOPOROSIS      August 19, 1998    7
            New guidelines for hormone
            replacement therapy (HRT)

                   The American Heart Association
                   is advising physicians to steer
  New data         clear of prescribing HRT for the
 contribute        sole purpose of preventing heart
to hormone         attack and stroke in women who
   therapy         already have cardiovascular
  confusion        disease.                    July 23, 2001

                                           CNN Medical Unit
                                         By Rhonda Rowland
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                             Estrogen & Strokes

                                   Oct. 24, 2001 — Estrogen
                                   pills fail to ward off new
                                   strokes in older women
                                   who have already suffered
                                   them, a study finds.
            The latest study, conducted by Catherine M. Viscoli and others
            from Yale University, was published in Thursday’s New England
            Journal of Medicine.
                                                             MSNBC NEWS SERVICES

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            Hormone therapy benefits questioned
            No proof of protection against some menopause illnesses

                          April 18, 2002 — A new report from
                          an international panel of experts,
                          sponsored by the National Institutes
                          of Health, raises serious questions
                          about many of the supposed benefits
                          of hormone replacement therapy.

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            Estrogen Plus Progestin Study
                   Due to Increased
                  Breast Cancer Risk,
                Lack of Overall Benefit
                NIH, Press Release, July 9, 2002

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    Women’s Health Initiative (WHI)
       Clinical Study Centers
               Seattle, WA
                               Minneapolis, MN
             Portland, OR
                                        Milwaukee, WI Detroit, MIBuffalo, NY
                                        Madison, WI                       Worcester, MA
                                     Iowa City, IA             Bronx, NY      Boston, MA
                                          Chicago, IL    Pittsburgh, PA       Pawtucket, RI
              Sacramento, CA                  Columbus, OH                  Stony Brook, NY
                  Reno, NV                   Cincinnati, OH              Newark, NJ
               Oakland, CA                                             Washington, DC
               Stanford, CA
                                            Memphis, TN             Winston-Salem, NC
                 Los Angeles, CA                                     Chapel Hill, NC
   Torrance, CA Orange, CA
                                                             Atlanta, GA
                     San Diego, CA
                            Tucson, AZ                 Birmingham, AL
             Honolulu, HI              San Antonio, TX
                                              Houston, TX       Gainesville, FL

                                                                  Miami, FL
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                        WHI HRT Study
                    Baseline Hypotheses

             Breast Cancer                                           Coronary Artery Disease

      Threshold Level                                         Threshold Level
  Early STOP=Clear Harm                                  Early STOP=Clear Benefit
                                                                            Additional Benefits:
 Additional Risks:                                                          • Osteoporosis Treatment
 • VTE                                 Plan to Study                        • Colon Cancer
                                                                            • Overall Mortality
                                         Until 2005
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  Adapted from: Writing Group for the Women’s Health Initiative. JAMA. 2002;288:321-333.
             Women’s Health Initiative
               Findings at Early Interruption
        29% Increase
    Coronary Artery Disease
     41% Increase
     26% Increase
        Breast Cancer

                                                                  Threshold Level
    Early STOP=Clear Harm
  VTE                                                                      Fracture Reduction
                                                                           Colon Cancer

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  Adapted from: Writing Group for the Women’s Health Initiative. JAMA. 2002;288:321-333.
                                         WHI HRT Study
                                  Effect of HRT on Event Rates
                                           Risks                      Benefits              Neutral
  in 10,000 Women Per Year

                             50    Additional Events                                                                Estrogen
       Number of Cases

                                  7       8        8         18
                             30                                        Events
                             20                                         6         5

                             10                                                            ---

                                   CHD   Stroke   Breast      VTE Colorectal Hip EndometrialDeaths
                                                  Cancer           Cancer Fracture Cancer

                                                       Adapted from: Women's Health Initiative. WHI HRT Update.
                                                       Available at: 2002.
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            … reactions from the
               other side of the Atlantic

                        The WISDOM trial is a major research
                     project, which will eventually involve over
                     16,000 post-menopausal women, aged 50-
                        69, in the UK and a further 6,000 from
                     Australia and New Zealand. To date, 5,000
                       women have been recruited in the UK.

                        The study is funded by the Medical
                       Research Council, the Department of
                      Health, the British Heart Foundation and
                                   other funders.

                       … WISDOM Study
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       … the Americans got the
  statistics wrong   ―… they had not conclusively
                         the increased risk of heart disease‖.

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            … but    U.K. Hormone Trial
                    to Pause for Review

                           For at least 3 months,
                     no new patients will be enrolled …

                              … an international
                      panel to recommend whether to
                       continue the trial in the face of
                       that prompted termination of a
                              similar U.S. study

                                     Science 2 AUGUST 2002

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            … more news

            … the bad news

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            … more news

              Estrogen raises ovarian
                    cancer risk
             July 16, 2002 — In another piece of the
                 increasingly complex hormone-
               replacement health puzzle, women
                given estrogen-only therapy after
            menopause ran a significantly higher risk
            of ovarian cancer, researchers reported

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                 Linked to

                 Increased Risk of
                               American College
             PHILADELPHIA,     of Chest Physicians
            November 8, 2001
                                   Annual Meeting
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            … more - this time good - news

                   … HRT reduces the risk

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            Replacement Therapy

                 Which system is next?
                    OSTEOPOROSIS         23
            Life without

              … what did Patti has to

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            … the Vanishing Promises
                    of HRT

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                                         By Jill Nelson
            Life without HRT             MSNBC CONTRIBUTOR

                          Yesterday I threw out my hormones.
                             I’d only been on them a year.
News on line             Unlike chocolate or sale catalogues,
                      I didn’t even have to run water over them
                                 to insure that I wouldn’t,
                              in a moment of desperation,
                           rescue them from the garbage bin
                             and promise to quit tomorrow.
                     I’m too concerned with my health for that.
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                                                July 12, 2002—
            EVISTA           Small increase in Bone Mineral
            Raloxifene HCI
                             Risk of spinal fractures
                              could be reduced by up to
                                            50 %.

                             OSTEOPOROSIS                 27
            … small increase in
                          Bone Mineral Density …

                           … and reduced risk of
                             OSTEOPOROSIS          28
            … we now know that it is true
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                                  JAMA 2002           288:321-333

                                             Cardiovascular and Coronary events
                                                after treatment with Raloxifene

            Raloxifene HCI    Raloxifene Therapy for 4 years

                                did not significantly affect

                             the risk of Cardiovascular Events

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?           … still confused?

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            … then, what about the
                 H.R.T Bar ...?

                     Where The Problems
                     Associated With The
                    Menopause Are Only A
                        Snack Away"
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            The active ingredients in the
              HRT Bar are high in plant
            Oestrogens (phytoestrogen)
               The various seed and fruit
               in the bars can help in Controlling:
                    Hot flushes
                    Mental agility
                    Delaying possible onset of Alzheimer's
                    Protecting breast tissue
                    Acting as antioxidants
                    Controlling cholesterol levels
                    Reducing loss of bone density

                               … according to the

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            … Increasingly, new research is
              questioning the purported
            health benefits of soy in adults,
              as well as raising concerns
               about adverse effects in

             JR Barrett
                  Soy and Children's Health: A Formula for Trouble?--
                  NIEHS Puts A New Face on Public Service.

             Environ Health Perspect 1 Jun 2002;110: A294-6

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  Combination Therapy
            Bisphosphonates + Estrogens
               there is no
                evidence that
                   give better
                   against fractures
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            News on line    Wednesday, July 25, 2001

                Osteoporosis Fracture Study
                       to Compare
                    Evista® & Fosamax®
                     The EVista Alendronate
                     Comparison (EVA) trial is the
                     first large-scale, head-to-head
                     study comparing a SERM and a
                     It's also the first head-to-head
                     fracture trial comparing
                     approved osteoporosis
8/19/2010            therapies.
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