Stephen Hough, Mediclinic Durbanville & Endocrine Unit ... · Stephen Hough, Mediclinic Durbanville...

transcript

Stephen Hough,

Mediclinic Durbanville &

Endocrine Unit Stellenbosch University

SASOG 2014

The European (IOF) Effort

The American (ASBMR) Effort

Normal Osteoporotic

Determinants of bone strength

Bone Mass (BMD)

Determinants of Bone Strength

Bone Quantity BMD

Bone Quality

• Macro- architecture

• Micro- architecture

• Bone Turnover

• Material Properties

- Geometry / size

• Cortical – porosity, thickness

• Trabecular – size, number, connectivity

Diagnosis of Osteoporosis: Methodology

Conventional Skeletal Radiology

Accurate measurement of arial BMD

Epidemiologic data to corroborate BMD data

Adequate assessment of vertebral morphology

p QCT; p DXA

Vertebral Fracture Assessment (VFA)

Genant classification of vertebral fractures.

Changes in Bone Density with Age

1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0

A g e ( Y e a r s )

Spine BMD

(g/cm2)

by DXA

White Women

Increase with adolescence

Peak bone mass

Plateau maintained

Menopausal bone loss (~1%-2% per year)

Age-related bone loss

(0.5% - 1.0% per year)

ASSOCIATION BETWEEN BMD AND RISK OF FRACTURE IN PMW

The association is continuous

Low BMD = high risk

-3 -2 -1 0 1

Hip Bone Density (T-score)

lative

LUMBAR (L1-L4) BMD

FEMORAL BMD

T-Score

T = −2.0 Z = −0.5

20 40 60 80 100

-4.0 0.720

BMD gm/cm2 Spine: L1-L4

WHO Criteria for Osteoporosis

in Postmenopausal Women

Normal BMD or BMC < 1SD below the young adult reference range

Low bone mass BMD or BMC 1 - 2.5SD below the mean of young healthy women

Osteoporosis BMD or BMC > 2.5SD below the mean of young healthy women

Severe osteoporosis BMD or BMC > 2.5SD below the mean of young healthy women and the presence of one or more fragility fractures

WHO Technical Report Series: B43,1994

Assessment of BMD in Premenopausal

WHO criteria and T-scores do not apply

Only Z-scores should be used: within 1 SD of norm = normal

decreased between 1 and 2 SD below the norm = uncertain or

intermediate

decreased > 2 SD is abnormal but, given the uncertainty re the relationship

between BMD and fracture risk in premenopausal women, is not sufficient

to confirm a diagnosis of osteoporosis.

Therefore, refer to a BMD Z-score of - ≤2SD as a

low BMD - not osteoporosis.

Diagnostic Criteria

Fragility fracture

Significantly low BMD (i.e. Z-score

decreased by ≥ 2 SD) plus one or more

well-known secondary causes of

osteoporosis.

WHO Criteria for Osteoporosis

in Postmenopausal Women

Normal BMD or BMC < 1SD below the young adult reference range

Low bone mass BMD or BMC 1 - 2.5SD below the mean of young healthy women

Osteoporosis BMD or BMC > 2.5SD below the mean of young healthy women

Severe osteoporosis BMD or BMC > 2.5SD below the mean of young healthy women and the presence of one or more fragility fractures

WHO Technical Report Series: B43,1994

WHO criteria based on data from white postmenopausal women employing axial DXA and cannot be extrapolated to other populations or techniques to measure BMD

No general agreement on skeletal sites to measure BMD, nor

most appropriate reference data to uses

Causes of a low BMD other than osteoporosis not considered

Bone quality not assessed Extraskeletal risk factors not addressed

Limitations of Mass-based Definitions of Osteoporosis

WHO criteria based on data from white postmenopausal women

employing axial DXA and cannot be extrapolated to other populations or techniques to measure BMD

No agreement on skeletal sites to measure BMD, nor most appropriate

reference data to use Bone quality not assessed Extraskeletal risk factors not addressed Causes of a low BMD other than osteoporosis not considered

Single BMD measurement lacks sensitivity (± 50%)

Limitations of Mass-based Definitions of Osteoporosis

Fracture Rates, Population BMD Distribution and Number of Fractures

BMD T-scores

1000 p

-years

>1.0 1.0 to 0.5

0.5 to 0.0

0.0 to –0.5

–0.5 to –1.0

–1.0 to –1.5

–1.5 to –2.0

–2.0 to –2.5

–2.5 to –3.0

–3.0 to –3.5

–3.5

Siris ES, et al.JAMA. 2001;286:2815-22.

Fracture Rate

Fracture Rates, Population BMD Distribution and Number of Fractures

# Fractures

BMD T-scores

>1.0 1.0 to 0.5

0.5 to 0.0

0.0 to –0.5

–0.5 to –1.0

–1.0 to –1.5

–1.5 to –2.0

–2.0 to –2.5

–2.5 to –3.0

–3.0 to –3.5 < –3.5

BMD distribution

Siris ES, et al. JAMA. 2001

Fracture Rate

50 60 70 70 80 age

- 2.5 SD - 2.5 SD

- 1.0 SD - 1.0 SD

T score

BMD T-scores

OSTEOPOROTIC FRACTURES

Fx/1000 p-yrs Women with Fxs

1 0.5 0 -0.5 -1 -1.5 -2 -2.5 -3 -3.5 0

Fracture Rate

Women with Fxs

75% 16% normal

57% osteopenia

FRACTURE RISK ASSESSMENT

Diagnosis of osteoporosis: low BMD or #

Only 10 – 44% of women with an osteoporotic fracture has a BMD T-score ≤ - 2.5

Sensitivity can be improved by:

lowering BMD threshold (e.g. T- score ≤ -2.0)

combining BMD + other risk factors

These other risk factors could include:

Clinical risk factors (CRFs)

Bone turnover (Biomarkers; Bx)

Others (QUS; Genetic markers)

CLINICAL RISK FACTORS (CRFs)

Advanced age, prior #, low BMI, family

history

Life style (e.g. alcohol, smoking, exercise)

Secondary osteoporoses (hypogonadism, GIOP)

Inadequate calcium / vitamin D nutrition; Falls

Generally lack sensitivity; may differ among patient populations. CRFs are additive in the prediction of fractures Local research necessary

INTEGRATED APPROACH TO FRACTURE RISK ASSESSMENT

Diagnostic Criteria vs Intervention Thresholds

Consider treatment in those with prior fragility fractures

Consider treatment when the DXA T-score is ≤ -2.5

Also consider treatment in subjects in whom a diagnosis of osteoporosis has not been confirmed, by employing an appropriate fracture risk assessment tool like SCORE, SOF fracture risk score, QFracture Score, FRAX etc

The FRAX® Tool

This large study (>60,000 subjects / > 12 study populations) identified a number of robust CRFs for the development of osteoporosis

Assessed the relative importance of the CRFs and their interactive and additive nature

Model output is the estimated 10-year probability of a hip and/or major osteoporotic fracture

Can be utilised ± BMD data

Major clinical risk factors identified

The FRAX® Tool

Major clinical risk factors identified:

Prior osteoporotic fracture

Advanced age

Family history of hip #

≥ 3/12 use of systemic GCs

Alcohol ≥ 3 drinks / day

Smoking

Low BMI

RA and other secondary osteoporoses

INTEGRATED APPROACH TO FRACTURE RISK ASSESSMENT

Diagnostic Criteria vs Intervention Thresholds

Consider treatment in those with prior fragility fractures

Consider treatment when the DXA T-score is ≤ -2.5

Also consider treatment in subjects in whom a diagnosis of osteoporosis has not been confirmed

Local incidence of osteoporosis in different populations needs to be assessed, following which a health economic strategy for the treatment of the disease needs to be formulated

NOFSA Recommendations

NON-PHARMACOLOGICAL MANAGEMENT

Adequate calcium (1200mg/d) and vitamin D (800IU/d)

Additional calcium and vitamin D (2,000 IU/d) during pregnancy/lactation

Serum 25(OH)D levels

Walking 30 - 40 min 3x/week

Limit alcohol < 3 units per day

Stop smoking

Avoid bone toxins

Prevent falls

PREVENTING FALLS

Medication – sedatives, hypnotics, etc.

Gait & balance

Cognition & affect

Weakness & mobility

Vision & depth perception

Environmental safety

Recurrent falls

Drug Therapy for Osteoporosis

• Anti- Resorptive Agents

- Calcium

- Vitamin D / Metabolites

- Sex Hormones / SERMS

- Calcitonins

- Bisphosphonates

• Formation Stimulating Agents

- Fluoride

- Anabolic Steroids

- Low-Dose Intermittent PTH

• Dual-/ Complex Action Drugs

- Strontium Salts

- Denosumab

Monitoring Therapy

• Clinical

– Disease progression

– Patient compliance

– Drug side effects

• Vertebral Imaging

• Biomarkers

• Routine BMD

– Techniques: DEXA

– Principles: The debate

Hormone Therapy (HT) for Osteoporosis

Initiate for specific indications, when not contra-indicated. For example the 50 - 60 yr woman with vasomotor or urogenital symptoms who is at risk of fracture

HT not recommended > age 60 yr.

Use doses known to provide fracture protection

Use most suitable therapeutic regimen

Monitor response to treatment, since 10 – 20% may lose BMD despite HT. Additional therapy required after D/C.

Current SERMS – use in selected cases

Tibolone – use limited by its safety profile

Phyto-oestrogens, progestins and testosterone cannot be recommended in women

Bisphosphonates (BPs) for Osteoporosis

One of the first-line treatments for osteoporosis in PMW, men and

Antifracture efficacy largely limited to patients at high risk – i.e.

those with T-scores ≤ -2.5

Precautions: empty stomach, water only, do not recline, not with

creatinine clearance < 30 ml/min

Osteonecrosis of the jaw (ONJ)

Duration of treatment, atypical fragility fractures, drug holidays

Antifracture efficacy of BP preparations – generic BPs

- Calcium

- Calcitonins

- Bisphosphonates

- Fluoride

- Anabolic Steroids

• Dual-Action Drugs

- Strontium Salts

J Med 2007;357:905-916

The Anabolic Window

Canalis et al 2007

Teriparatide (PTH 1-34) for Osteoporosis

To be used only per specific indication, when not contra-indicated.

20 μg/d sc, for 18 months. Monitor serum and urine calcium

If taking HT or SERM, merely add the teriparatide. Less clear

whether to add or switch to teriparatide when taking a BP

Preserve bone mass gained when completing 18/12 course of

teriparatide

- Calcium

- Calcitonins

- Bisphosphonates

- Fluoride

- Anabolic Steroids

• Dual-Action Drugs

- Strontium Salts

Strontium Ranelate for Osteoporosis

One of the first-line treatments for postmenopausal osteoporosis

Long-term antifracture data available

Effective in patients with osteoporosis, as well as those with

osteopenia

Effective in the very old (>80yr)

Contra-indicated in those with uncontrolled hypertension, known

CVD or at risk of VTE

DRESS syndrome

Rational Choice of Therapy

• Nature of the Osteoporosis - Severity of the osteopenia

- Presence of fractures

- Skeletal sites

- Specific circumstances

- Skeletal sites

- Response to therapy

• The Patient - Healthy, requiring a bone-specific drug

- Menopausal symptoms

- Risk of breast cancer

- Frail elderly / Life expectancy

- Personal preferences / Willingness

- Skeletal sites

- Response to therapy

• The Patient - Healthy, requiring a bone-specific drug

- Menopausal symptoms

- Risk of breast cancer

- Frail elderly / Life expectancy

- Personal references / Willingness

• Cost-Effectiveness / Side-Effects

• Availability

Monitoring Therapy

• Clinical

– Disease progression

– Patient compliance

– Drug side effects

• Vertebral Imaging

• Biomarkers

• Routine BMD

– Techniques: DEXA

– Principles: The debate

Stephen Hough, Mediclinic Durbanville & Endocrine Unit ... · Stephen Hough, Mediclinic Durbanville...

Documents