Prevention of Osteoporosis: The Role of The Gynecologist Dr

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Prevention of OsteoporosisThe Role of The
Gynecologist

• Dr. Mohamed El SherbinyMD Ob. Gyn. Senior
  Consultant
• Damietta, Egypt

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Osteoporosis
The Nightmare Of Post-menopause
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Pathophysiology
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Lifetime Changes In Bone Mass
50 of cancellous 35 of cortical bone mass are
lost over a lifetime
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Bone Remolding
Osteoblasts deposit new lamellar bone.
Osteocytes are osteoblasts trapped in the
matrix Osteoclasts resorb matrix
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Nutritional status
Genetic factors
Peak Bone Mass
Gonadal status
Physical activity
Determinants Of Peak Bone Mass
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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.
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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
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Microarchitectural deterioration
Low bone density
Normal bone
Osteoporosis
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Osteoporosis Sites

• Osteoporotic fractures can occur at any site.
• The most common sites are
• Lumbar thoracic spines
• Proximal femur.
• Distal radius

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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

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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
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Consequences of Hip Fractures

• 520 mortality within 1 year
• 20 severely impaired mobility, requiring
  long-term nursing care
• 50 do not regain previous mobility

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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
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DEXA
It employs two x-ray beams of different energy
levels
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DEXA
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DEXA
1
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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.
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Normal
Ostopenia
Osteoporosis
The Role of Densitometry
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Tests Other Than DEXAPeripheral bone
densitometry devices

• Quantitative ultrasonography .
• Single-energy x-ray absorptiometry.
• Peripheral DEXA
• Peripheral quantitative computed tomography.

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Quantitative Ultrasound for the Assessment of
Osteoporosis
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Tests Other Than DEXAPeripheral 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
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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

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Nutritional status
Genetic factors
Peak Bone Mass
Gonadal status
Physical activity
Determinants Of Peak Bone Mass
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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

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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.

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Female Athlete Triad
Adolescent Girls

• Disordered Eating
• Amenorrhea
• Osteoporosis

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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
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Role of Gynecologist

• I- At adolescent adult age
• B-To reduce bone loss secondary to drugs
• Gn Rh Analogue.
• Dopamine Agonist
• Glucocortocoied
• Depo-provera??

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GNRH Agonist For EndometriosisCan 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
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GNRH Agonist For EndometriosisCan 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.
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Role of Gynecologist

• II- At Peri-menopause.
• To Prevent osteoporosis in high risk group
• 1-Screening
• 2-Managment

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• 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
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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
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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
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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
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Treatment

• Exercise
• Diet
• Drugs

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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
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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
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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
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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
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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)
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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
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Calcitonin (Miacalcic 100IU/d IM .sc or 200IU/d
nasal
65
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Parathyroid Hormone Fortéo 20micg/d for 2y
National Osteoporosis Foundation. 2003 The
Medical Journal of Australia 2004
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Osteoporosis Problem Solving Cases
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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.
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Osteopenia

• T score -2

The result of DEXA is 2 what is the treatment
option of choice?
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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?
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As the patient has significant hot flushes and
has no contraindication HRT may be the option
of choice
What Is The Treatment Of Choice?
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So far there are false perceptions regarding the
use of HRT -even in big authorities - due
to1-Old data 2-Incomplete analysis of the data
(subgroup)
Discussion
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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.

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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

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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
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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
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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
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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

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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
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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)
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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
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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
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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)
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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)
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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
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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
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Raloxifene

• Raloxifene is not recommended as a treatment
  option for the primary prevention of osteoporotic
  fragility fractures in postmenopausal women.

NICE October 2008
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Osteoporosis Therapy AlgorithmPostmenopausal
Women
Bisphosphonates Or Strontium Ranelate
50 55 60 65
70 75 80 85
90
Lower
Higher
-2.5
BMD (T-score)
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Osteoporosis Therapy AlgorithmPostmenopausal
Women
Tibolone
Bisphosphonates Or Strontium Ranelate
50 55 60 65
70 75 80 85
90
Lower
Higher
-2.5
BMD (T-score)
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Damietta
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Thank You