osteoporosis

Prevention of Osteoporosis:

The Role of The Gynecologist

www.freelivedoctor.com

The Nightmare Of Post-menopause

Osteoporosis


Pathophysiology


Lifetime Changes In Bone Mass

50% of cancellous &35% of cortical bone mass are lost over a lifetime


Bone Remolding

Osteoblasts deposit new lamellar bone. Osteocytes are osteoblasts trapped in the matrixOsteoclasts resorb matrixwww.freelivedoctor.com

Determinants Of Peak Bone Mass

Peak Bone Mass

Physical activity Gonadal status

Nutritional statusGenetic factors


Peak Bone MassThe 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 1992;327:82–7.

Bonjour ,et al. J Clin Invest 1997;99:1287–94.www.freelivedoctor.com

Osteoporosis: DefinitionOsteoporosis is a progressive, systemic

disorder characterized by:

Low bone mass

Micro-architectural deterioration of bone tissue

Increase in bone fragility and susceptibility to fracture.

National Institute for Clinical Excellence (NICE) guidance 160 October 2008

WHO 1994


Normal bone Osteoporosis

Microarchitectural deterioration

Low bone density


Osteoporosis: Sites

Osteoporotic fractures can occur at any site.

The most common sites are:

Lumbar & thoracic spines

Proximal femur.

Distal radiuswww.freelivedoctor.com

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

50 60 70 80

40

30

20

10

Vertebrae

Hip

Wrist

Age (Years)

An

nu

al in

cid

ence

per

10

00 w

om

en


The Magnitude Of The ProblemIn women > 50 years, the lifetime risk of:

• Vertebral fracture is 1/3

• Hip fracture is 1/5

NICE guidance 160 October 2008www.freelivedoctor.com

5–20% mortality within 1 year

20% severely impaired

mobility, requiring long-term

nursing care

50% do not regain previous

mobility

Consequences of Hip Fractures


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 2004www.freelivedoctor.com

DEXAIt employs two x-ray beams of different energy levels


DEXA


1

DEXA


•T score ≥ -1

•T score -1 to -2.5

•T score < -2.5

Normal

Osteopenia

Osteoporosis

WHO Classification of BMD using (DEXA) scan

•T score < -2.5+ H. of fracture Severe Osteoporosis

T score represents the number of SD a patient is above or below the mean BMD of a young adult.


The Role of Densitometry

Normal

Ostopenia

Osteoporosis


Quantitative ultrasonography .

Single-energy x-ray absorptiometry.

Peripheral DEXA

Peripheral quantitative computed

tomography.

Tests Other Than DEXAPeripheral bone densitometry devices


Quantitative Ultrasound for the Assessment of Osteoporosis


They are less expensive and have low

radiation exposure, however :

Tests Other Than DEXAPeripheral bone densitometry devices

They have low precision and accuracy.

They measure peripheral bone only.

Cannot replace DEXA scans .


What Is The Role of The Gynecologist ?

I- At Adolescent & Adult AgeTo achieve a peak bone mass

II- At Peri-menopauseTo prevent osteoporosis in high risk group

III-At Late Post-menopause? To prevent age related osteoporosis (>65y)Usually it is an orthopedic role


Determinants Of Peak Bone Mass

Peak Bone Mass

Physical activity Gonadal status

Nutritional statusGenetic factors


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


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.


Female Athlete Triad Disordered Eating

Amenorrhea

Osteoporosis

Adolescent Girls


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 1990;76:585.

Emans et al. Pediatric & Adolescent Gynecology, 5th Edit.2005 www.freelivedoctor.com

Role of Gynecologist I- At adolescent & adult age : B-To reduce bone loss

secondary to drugs:Gn Rh Analogue.Dopamine AgonistGlucocortocoied Depo-provera??


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 www.freelivedoctor.com

• 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.

Sagsveen M et al , Cochrane Database Syst Rev 2003;(4):CD001297.

Level 1a

GNRH Agonist For EndometriosisCan BMD loss be prevented by using ‘add-

back’ therapy?


Role of Gynecologist

II- At Peri-menopause. To Prevent osteoporosis in high risk group:

1-Screening

2-Managment


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 Guideline2009www.freelivedoctor.com

Age >65 years

Early menopause (< 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

Risk Factors For OsteoporosisMajor Risk Factors

SOGC Clinical Practice Guideline2009


Rheumatoid arthritisHistory of clinical hyperthyroidismLong-term anticonvulsant therapyLow dietary calcium intakeSmokingExcessive alcohol intakeExcessive caffeine intakeWeight < 57 kgWeight loss: 10% of weight at age 25 yearsLong-term heparin therapy

Minor risk factors

SOGC Clinical Practice Guideline2009www.freelivedoctor.com

When Is Treatment Indicated??

T score < -2 & No fractures

T score < -1.5 in with a history

of fracture or other risk factors

T score < -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 2004www.freelivedoctor.com

Treatment•Exercise

•Diet

•Drugs www.freelivedoctor.com

THE ROLE OF EXERCISE

Studies have shown that weight-bearing exercise and increased muscle mass lead to the development of increased bone mass.


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 Guideline2009www.freelivedoctor.com


For postmenopausal, intake of 1500mg of elemental calcium & 800 IU/d of vitamin D are recommended.

The Society of Obstetricians and Gynaecologists of Canada.(SOGC) Clinical Practice Guideline2009

Grade B



Calcium and vitamin D alone are insufficient to prevent fracture in those with osteoporosis.

The Society of Obstetricians and Gynaecologists of Canada.(SOGC) Clinical Practice Guideline2009

Grade B


What are the pharmacotherapy ? Medications available for osteoporosis1- 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)


Spine Hip 50% 50%

50% 40% 30% 30% HRT/Tibolone >35% >30% > 30%

Raloxifene:Evista60 mg /d 34% 21%

Parathyroid Hormone Fortéo 20micg/d for 2y

65% 45%National Osteoporosis Foundation.; 2003 & The Medical Journal of Australia 2004

Drugs used for prevention & treatment of osteoporosis

Alendronate :Fosomax5mg/d or35mg/w

Calcitonin (Miacalcic100IU/d IM .sc or 200IU/d nasal

Other non spine

Strontium Ranelate(Protelos, 2g)

30% 30% 30%

Risedronate: Actonel5mg/d or 35mg/w


Osteoporosis: Problem Solving

Cases


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.www.freelivedoctor.com

•T score -2 Osteopenia

The result of DEXA is – 2 what is the treatment option of choice? www.freelivedoctor.com

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?


As the patient has significant hot flushes and has no

contraindication :HRT may be the option of

choice

What Is The Treatment Of Choice?


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


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.


False PerceptionsOfficial 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:

FailedAre contraindicated Not tolerated


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 www.freelivedoctor.com


It is therefore suggested that, in 50–59-year-old postmenopausal women, HRT is a cost-effective first-line treatment in the prevention of osteoporotic fractures.



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.


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

Case 2


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

What is The Treatment of Choice?


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 .

Carpenter et al Oncologist 2007 Jan;12(1):124-35.RCT(Doub.blinde)

Evanc et al Obstet Gynecol. 2005 Jan;105(1):161-6. RCTwww.freelivedoctor.com

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 (>2 years) trials.

New Zealand Guidelines Group March 2004

(Grade A)

Use of tibolone may be associated with an increased risk of breast cancer. Million Women Study 2003


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

Tibolone (Previous 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 2008;359:697–708 (RCT 4538 women 60 - 85 years)

Tibolone in Breast Cancer(Recent View )


TiboloneTibolone should be used with caution in

elderly women (> 70 years ).

That is the age at which hormone therapy is critical, as was also shown in the Women’s Health Initiative (WHI) studies with the effects of conventional HRT

Long-Term Intervention on Fractures with Tibolone (LIFT Study)

N Engl J Med 2008;359:697–708 (RCT 4538 women 60 - 85 years) www.freelivedoctor.com

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 Feb;10(2):135-46. Multicenter (3098 ptients)245 centres in 31 countries double-blind RCT

Tibolone in Breast Cancer(Recent View )But


For hot flushes 1-Venlafaxine= (Effexor) 2-Tibolone very short time under strict follow up for hot flushesFor prevention of osteoporosis:

1-Bisphosphonates Or 2-Strontium Ranelate

What is The Treatment of Choice?


RaloxifeneRaloxifene is not recommended

as a treatment option for the primary prevention of osteoporotic fragility fractures in postmenopausal women.

NICE October 2008www.freelivedoctor.com

Raloxifene

PTH

CalcitoninHRTHRT

HRTHRT

During Hot Flushes

Post Vasomotor SymptomsPre fracture

Post Fracture

Risk of Fracture

AGE

At Risk/Osteopenia Osteoporosis Severe OsteoporosisSTAGE

LowerHigher-2.5BMD (T-score)

Bisphosphonates Or Strontium Ranelate

Osteoporosis Therapy AlgorithmOsteoporosis Therapy AlgorithmPostmenopausal WomenPostmenopausal Women

50 55 60 65 70 75 80 85 90


Raloxifene

PTH

CalcitoninHRTHRT

HRTHRT

During Hot Flushes

Post Vasomotor SymptomsPre fracture

Post Fracture

Risk of Fracture

AGE

At Risk/Osteopenia Osteoporosis Severe OsteoporosisSTAGE

LowerHigher-2.5BMD (T-score)

Bisphosphonates Or Strontium Ranelate

Osteoporosis Therapy AlgorithmOsteoporosis Therapy AlgorithmPostmenopausal WomenPostmenopausal Women

50 55 60 65 70 75 80 85 90

Tibolone


osteoporosis

Documents

bone fragility

cortical bone mass

bone mineral density

metabolic bone diseases

bone loss secondary

osteoporosis length

definition osteoporosis

assessment of osteoporosis