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Prevention of Osteoporosis: The Role of The Gynecologist Dr

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Prevention of Osteoporosis: The Role of The Gynecologist Dr. Mohamed El Sherbiny MD Ob.& Gyn. Senior Consultant Damietta, Egypt For hot flushes 1-Venlafaxine ... – PowerPoint PPT presentation

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Title: Prevention of Osteoporosis: The Role of The Gynecologist Dr


1
Prevention of Osteoporosis The Role of The
Gynecologist
  • Dr. Mohamed El Sherbiny MD Ob. Gyn. Senior
    Consultant
  • Damietta, Egypt

2
Osteoporosis
The Nightmare Of Post-menopause
3
Pathophysiology
4
Lifetime Changes In Bone Mass
50 of cancellous 35 of cortical bone mass are
lost over a lifetime
5
Bone Remolding
Osteoblasts deposit new lamellar bone.
Osteocytes are osteoblasts trapped in the
matrix Osteoclasts resorb matrix
6
Nutritional status
Genetic factors
Peak Bone Mass
Gonadal status
Physical activity
Determinants Of Peak Bone Mass
7
Peak Bone Mass
  • The peak bone mass attained is a major
    determinant of subsequent bone mass and fracture
    risk in later life.

Johnston, et al.. N Engl J Med 1992327827.
Bonjour ,et al. J Clin Invest 199799128794.
8
Osteoporosis Definition
  • Osteoporosis is a progressive, systemic disorder
    characterized by
  • Low bone mass
  • Micro-architectural deterioration of bone tissue
  • Increase in bone fragility and susceptibility to
    fracture.

WHO 1994
National Institute for Clinical Excellence (NICE)
guidance 160 October 2008
9
Microarchitectural deterioration
Low bone density
Normal bone
Osteoporosis
10
Osteoporosis Sites
  • Osteoporotic fractures can occur at any site.
  • The most common sites are
  • Lumbar thoracic spines
  • Proximal femur.
  • Distal radius

11
Incidence Rates for Vertebral, Wrist Hip
Fractures in Women after Age 50
  • Wasnich RD, Primer on the Metabolic Bone Diseases
    and Disorders of Mineral Metabolism. 4th edition,
    1999

12
The Magnitude Of The Problem
  • In women gt 50 years, the lifetime risk of
  • Vertebral fracture is 1/3
  • Hip fracture is 1/5

NICE guidance 160 October 2008
13
Consequences of Hip Fractures
  • 520 mortality within 1 year
  • 20 severely impaired mobility, requiring
    long-term nursing care
  • 50 do not regain previous mobility

14
What is the technical standard for measuring BMD
?
  • Dual-Energy X-ray Absorptiometry (DEXA) is the
    technical standard Why??
  • It measures at important sites of osteoporotic
    fractures.
  • It has high precision and accuracy.
  • It is relatively inexpensive and has modest
    radiation exposure.

ACOG Guideline January 2004
15
DEXA
It employs two x-ray beams of different energy
levels
16
DEXA
17
DEXA
1
18
WHO Classification of BMD using (DEXA) scan
Normal
  • T score -1

Osteopenia
  • T score -1 to -2.5

Osteoporosis
  • T score lt -2.5

Severe Osteoporosis
  • T score lt -2.5
  • H. of fracture

T score represents the number of SD a patient is
above or below the mean BMD of a young adult.
19
Normal
Ostopenia
Osteoporosis
The Role of Densitometry
20
Tests Other Than DEXA Peripheral bone
densitometry devices
  • Quantitative ultrasonography .
  • Single-energy x-ray absorptiometry.
  • Peripheral DEXA
  • Peripheral quantitative computed tomography.

21
Quantitative Ultrasound for the Assessment of
Osteoporosis
22
Tests Other Than DEXA Peripheral bone
densitometry devices
  • They are less expensive and have low radiation
    exposure, however
  • They have low precision and accuracy.
  • They measure peripheral bone only.
  • Cannot replace DEXA scans .

ACOG Guideline January 2004
23
What Is The Role of The Gynecologist ?
  • I- At Adolescent Adult Age
  • To achieve a peak bone mass
  • II- At Peri-menopause
  • To prevent osteoporosis in high risk group
  • III-At Late Post-menopause?
  • To prevent age related osteoporosis (gt65y)
  • Usually it is an orthopedic role

24
Nutritional status
Genetic factors
Peak Bone Mass
Gonadal status
Physical activity
Determinants Of Peak Bone Mass
25
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26
Role of Gynecologist
  • I- At adolescent Adult age
  • A-To achieve a peak bone mass in susceptible
    group.
  • Late menarche
  • Menstrual interruptions/irregularities
  • Pregnancy
  • Lactation

27
Role of Gynecologist
  • I- At adolescent Adult age
  • A-To achieve a peak bone mass in susceptible
    group.
  • B-To reduce bone loss secondary to drugs.

28
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29
Female Athlete Triad
Adolescent Girls
  • Disordered Eating
  • Amenorrhea
  • Osteoporosis

30
Turner Syndrome
  • - 90 of women had osteopenia or osteoporosis
  • - Length of estrogen treatment and BMI showed a
    positive association with bone mineral density.

Emans et al. Obstet Gynecol 199076585.
Emans et al. Pediatric Adolescent Gynecology,
5th Edit.2005
31
Role of Gynecologist
  • I- At adolescent adult age
  • B-To reduce bone loss secondary to drugs
  • Gn Rh Analogue.
  • Dopamine Agonist
  • Glucocortocoied
  • Depo-provera??

32
GNRH Agonist For Endometriosis Can BMD loss be
prevented by using add-back therapy?
  • The use of a GnRH agonist with add-back
    (oestrogen progestagen) therapy protects
    against bone mineral density loss at the lumbar
    spine during treatment and for up to 6 and 12
    months after treatment, respectively.

ESHRE Guideline 2005 RCOG 2006 Grade A
33
GNRH Agonist For Endometriosis Can BMD loss be
prevented by using add-back therapy?
  • GnRH agonist add-back therapy for at least 6
    months BMD was significantly higher compared to
    a GnRH agonist alone
  • Hypoestrogenic side effects were significantly
    less with add-back.
  • Progestagen only addback is not protective
  • There is insufficient evidence regarding
    calcium-regulating agents.

Level 1a
Sagsveen M et al , Cochrane Database Syst Rev
2003(4)CD001297.
34
Role of Gynecologist
  • II- At Peri-menopause.
  • To Prevent osteoporosis in high risk group
  • 1-Screening
  • 2-Managment

35
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36
  • Testing of BMD is justified when there is
  • One major risk factor for osteoporosis or
  • Tow minor risk factors for osteoporosis

The Society of Obstetricians and Gynaecologists
of Canada.(SOGC) Clinical Practice Guideline2009
37
Major Risk Factors
Risk Factors For Osteoporosis
  • Age gt65 years
  • Early menopause (lt 45 Years)
  • Hypogonadism (Spontaneous or iatrogenic)
  • Vertebral compression fracture
  • Fragility fracture after age 40 Ys
  • Family history of osteoporotic fracture
  • Glucocorticoid therapy for 3 months
  • Malabsorption syndrome
  • Primary hyperparathyroidism
  • Propensity to fall
  • Osteopenia apparent on radiograph

SOGC Clinical Practice Guideline2009
38
Minor risk factors
  • Rheumatoid arthritis
  • History of clinical hyperthyroidism
  • Long-term anticonvulsant therapy
  • Low dietary calcium intake
  • Smoking
  • Excessive alcohol intake
  • Excessive caffeine intake
  • Weight lt 57 kg
  • Weight loss 10 of weight at age 25 years
  • Long-term heparin therapy

SOGC Clinical Practice Guideline2009
39
When Is Treatment Indicated??
  • T score lt -2 No fractures
  • T score lt -1.5 in with a history
  • of fracture or other risk factors
  • T score lt -0.5 in women with
  • a history of fracture and other risk factors.
  • T score 1 unit higher in patients receiving
    glucocorticoid drugs.

Board of Osteoporosis New Zealand 2004
ACOG Guideline January 2004
40
Treatment
  • Exercise
  • Diet
  • Drugs

41
THE ROLE OF EXERCISE
  • Studies have shown that weight-bearing exercise
    and increased muscle mass lead to the development
    of increased bone mass.

ACOG Guideline January 2004
42
Calcium Vitamin D (At Any Age)
  • Adequate calcium and vitamin D supplementation is
    key to ensure prevention of progressive bone
    loss.

Canadian Task Force on Preventive Health Care 2004
The Society of Obstetricians and Gynaecologists
of Canada.(SOGC) Clinical Practice Guideline2009
43
Calcium Vitamin D (At Any Age)
  • For postmenopausal, intake of 1500mg of elemental
    calcium 800 IU/d of vitamin D are recommended.

Grade B
The Society of Obstetricians and Gynaecologists
of Canada.(SOGC) Clinical Practice Guideline2009
44
Calcium Vitamin D (At Any Age)
  • Calcium and vitamin D alone are insufficient to
    prevent fracture in those with osteoporosis.

Grade B
The Society of Obstetricians and Gynaecologists
of Canada.(SOGC) Clinical Practice Guideline2009
45
What are the pharmacotherapy ?
  • Medications available for osteoporosis
  • 1- Calcium Vitamin D
  • 2- Estrogen ( progesagen)
  • 3- Bisphosphonates
  • Alendronate (Fosamax)
  • Risedronate (Actonel)
  • 5- Selective estrogen- receptor modulators (SERM)
  • Raloxifene. (Evista)
  • Tibolone.(Livial) STEAR Selective Tissue
    Estrogenic Activity Regulator
  • 6- Calcitonin (Miacalcic)
  • 7- Parathyroid Hormone

4- Strontium Ranelate(Protelos, 2g)
46
Drugs used for prevention treatment of
osteoporosis
Other non spine
Spine Hip
50 50
50
Alendronate Fosomax 5mg/d or35mg/w
40 30
30
Risedronate Actonel 5mg/d or 35mg/w
30 30 30
Strontium Ranelate (Protelos, 2g)
HRT/Tibolone gt35 gt30 gt 30
RaloxifeneEvista60 mg /d 34
21
Calcitonin (Miacalcic 100IU/d IM .sc or 200IU/d
nasal
65
45
Parathyroid Hormone Fortéo 20micg/d for 2y
National Osteoporosis Foundation. 2003 The
Medical Journal of Australia 2004
47
Osteoporosis Problem Solving Cases
48
A 53-year-old G6P4 woman complains of Amenorrhea
11 months with 10-15 hot flushes/day. She is
afraid as her mother has died 9 months after
fracture neck femur at the age of 67 years BP
120/75, weight 74 kg , height 171cm (BMI
25kg/m2) Breast, abdominal pelvic examinations
revealed no abnormal findings.
49
Osteopenia
  • T score -2

The result of DEXA is 2 what is the treatment
option of choice?
50
As the patient has significant hot flushes and
has no contraindication HRT may be the option
of choice
What Is The Treatment Option Of Choice?
51
As the patient has significant hot flushes and
has no contraindication HRT may be the option
of choice
What Is The Treatment Of Choice?
52
So far there are false perceptions regarding the
use of HRT -even in big authorities - due
to 1-Old data 2-Incomplete analysis of the data
(subgroup)
Discussion
53
False Perceptions
  • HRT should not be used for bone protection
    because of its unfavorable safety profile.
  • HRT is not as effective in reducing fracture
    risk as other products, e.g. bisphosphonates.

54
False Perceptions
  • Official recommendations by some health
    authorities as Agency for the Evaluation of
    Medicinal Products (EMEA) FDA limit the use of
    HRT to
  • 1- Symptomatic women
  • 2- A second-line alternative when other
    medications
  • Failed
  • Are contraindicated
  • Not tolerated

55
What Is The Recent Evidence ?
  • Overall, HRT is effective in the prevention of
    all osteoporosis-related fractures. A
  • There is no evidence to suggest that
    bisphosphonates or any other antiresorptive
    therapy are superior to HRT.

International Menopause Society (Zürich
Summit)2008
56
What Is The Recent Evidence ?
  • It is therefore suggested that, in 5059-year-old
    postmenopausal women, HRT is a cost-effective
    first-line treatment in the prevention of
    osteoporotic fractures.

International Menopause Society (Zürich
Summit)2008
57
What Is The Recent Evidence ?
  • Even lower than standard-dose preparations
    maintain a positive influence on bone indices
    such as bone mineral density. A
  • HRT has a positive effect on osteoarthritis and
    the integrity of intervertebral disks.

International Menopause Society (Zürich
Summit)2008
58
Case 2
  • A 45-year-old P2 woman complains of amenorrhea
    one year with 15-20 hot flushes/day.
  • She has a history of L. radical mastectomy for
    breast cancer 7 years ago with complete cure.
  • BP 130/85, weight 60 kg. height 163cm,
    Right Breast, abdominal pelvic
    examinations revealed no abnormal findings.
  • Fasting sugar 95 mg/dl within normal lipid
    profile

59
What is The Treatment of Choice?
HRT is not recommended for cases with cured
cancer breast even after 5 years except in some
exceptional condition for a very short time under
strict follow up
There are other 2 lines of therapy
60
1-Venlafaxine (Effexor)
  • Venlafaxine (Effexor) Selective Serotonin
    Reuptake Inhibitor (SSRI) 75mg/d
  • A newer antidepressant used to reduce hot flushes
    and improve mood at menopause.
  • Although venlafaxine resulted in modest and acute
    reductions in hot flushes with few side effects,
    it may not be tolerable to some patients for
    long-term .

Evanc et al Obstet Gynecol. 2005
Jan105(1)161-6. RCT
Carpenter et al Oncologist 2007
Jan12(1)124-35.RCT(Doub.blinde)
61
Tibolone (Previous view)
  • Tibolone alleviates the severity and reduces the
    frequency of hot flushes .It has been shown to be
    effective for vaginal dryness .
  • The potential harms (cv Breast cancer of
    treatment have not yet been thoroughly assessed
    with long-term randomized (gt2 years) trials.

(Grade A)
Use of tibolone may be associated with an
increased risk of breast cancer .
Million Women Study 2003
New Zealand Guidelines Group March 2004
62
Tibolone (Previous view)
  • Tibolone has been demonstrated to prevent
    postmenopausal bone loss and increase BMD,
    however, currently no trials have evaluated
    whether tibolone decreases the risk of fracture.

Australian Family Physician Vol. 33, No. 3, March
2004
63
Tibolone in Breast Cancer (Recent View )
  • Tibolone reduces the risk of osteoporotic
    fractures similar to other treatments such as
    HRT, bisphosphonates and raloxifene
  • Tibolone reduces the risk of invasive breast
    cancer similar to raloxifene and tamoxifen

Long-Term Intervention on Fractures with Tibolone
(LIFT Study) N Engl J Med 2008359697708 (RCT
4538 women 60 - 85 years)
64
Tibolone
  • Tibolone should be used with caution in elderly
    women (gt 70 years ).
  • That is the age at which hormone therapy is
    critical, as was also shown in the Womens Health
    Initiative (WHI) studies with the effects of
    conventional HRT

Long-Term Intervention on Fractures with Tibolone
(LIFT Study) N Engl J Med 2008359697708 (RCT
4538 women 60 - 85 years)
65
Tibolone in Breast Cancer (Recent View )
But
  • There were more cancer recurrences in those
    taking tibolone compared with those on placebo
    (15 v 10), causing the trial to close early.
  • Overall mortality, cardiovascular events and
    gynaecological cancers were no different but the
    breast cancer recurrence rates make it unsafe to
    use tibolone in these circumstances.

Kenemanas et al Lancet Oncol. 2009
Feb10(2)135-46. Multicenter (3098 ptients)245
centres in 31 countries double-blind RCT
66
What is The Treatment of Choice?
For hot flushes 1-Venlafaxine (Effexor)
2-Tibolone very short time under strict follow
up for hot flushes For prevention of
osteoporosis 1-Bisphosphonates Or 2-Strontium
Ranelate
67
Raloxifene
  • Raloxifene is not recommended as a treatment
    option for the primary prevention of osteoporotic
    fragility fractures in postmenopausal women.

NICE October 2008
68
Osteoporosis Therapy Algorithm Postmenopausal
Women
Bisphosphonates Or Strontium Ranelate
50 55 60 65
70 75 80 85
90
Lower
Higher
-2.5
BMD (T-score)
69
Osteoporosis Therapy Algorithm Postmenopausal
Women
Tibolone
Bisphosphonates Or Strontium Ranelate
50 55 60 65
70 75 80 85
90
Lower
Higher
-2.5
BMD (T-score)
70
Damietta
71
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