Glucocorticoid-Induced Osteoporosis (GIO) Nguyen Thy Khue, MD, PhD Department of Endocrinology, HoChiMinh City University of Medicine and Pharmacy.

Glucocorticoid-Induced Osteoporosis (GIO)

Nguyen Thy Khue, MD, PhD

Department of Endocrinology,

HoChiMinh City University of Medicine and Pharmacy

Epidemiology of GIO

• Prevalence of oral glucocorticoid use ~1% of the adult population1

2.5% in individuals aged 70-79

• Up to 350,000 individuals in UK at risk of fractures due to glucocorticoid use

(Van Staa TP et al, 2000)

GC in developing countries

• Prevalence: unknown.

• Glucocorticoid can be purchased over the counter.

Projected number of glucocorticoid use among 50+

0

100

200

300

400

500

600

700

0.005 0.010 0.015 0.020 0.025 0.050 0.100

Men Women

Prevalence of using glucocorticoid Num

ber

of in

divi

dual

s us

ing

gluc

ocor

ticoi

d (

x100

0)

Mechanism of Corticosteroid Induced Osteoporosis

(Segal L G et al. 1997)D1202

Osteoporosis

Osteoblastbone

formation

PTH?

Effects ongrowth hormones& growth factors

gastrointestinalcalcium absorption

urinary calciumexcretion

calcium

Corticosteroids

osteoclastbone resorption

Sex hormone effects: adrenal androgens

oestrogen

testosterone

musclemass

-6.0%

-5.0%

-4.0%

-3.0%

-2.0%

-1.0%

0.0%

3 6 9 12

*

*

*

* p <0.01 vs. baseline

Effect of steroids on bone mineral density%

Bon

e ch

ange

vs

base

line

( Mulder H et al. 1994)

D1202

Months

Factors associated with fracture risk with GC Rx

• Age• BMD

– Initial & subsequent to GC Rx.– Postmenopausal women – highest risk.

• Glucorticoid dose: cumulative & mean daily dose.

• Duration of exposure.• Underlying diseases.

Fracture type and the use of Glucocorticoid

Fracture type Gender Corticosteroid use

Prior fracture

Any fracture M 1.7 (1.1–2.5) 1.7 (1.4–2.1 )

F 1.4 (1.2–1.6) 1.7 (1.6–1.9)

Osteoporotic

fracture

M 2.2 (1.4–3.3) 1.7 (1.4–2.1)

F 1.4 (1.2–1.7) 1.7 (1.6–1.9)

Hip fracture M 2.6 (0.9–7.5) 1.7 (1.0–2.9)

F 2.1 (1.4–3.1) 1.7 (1.3–2.1)

(Kanis JA, et al, 2004)

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

0.020 0.025 0.050 0.100

Men Women

0

500

1000

1500

2000

2500

3000

0.020 0.025 0.050 0.100

Men Women

Projected number of GC-induced fractures per year for men and women aged 50+

Prevalence of using glucocorticoid

Any fracture Hip fracture

Incidence of non-vertebral fractures (per 100 p-yrs) in women

(van Staa et al, 2000)

0

1

2

3

4

5

6

7

8Control< 2.5mg

2.5-7.5mg>7.5 mg

18-34 35-44 45-54 55-64 65-74 75-84 > 85

Age (years)

244.235 oral GC users244.235 controls58.6% female

Incidence of non-vertebral fracture before, during and after steroid therapy

0.5

1.0

1.5

2.0

2.5 Before

During

After

Months

24 1 6 60 3 30

van Staa JBMR 2000

3 to 6months

Time 3 to 6months

Bone Strength

Steroid therapy

A + B C D + E

A = osteocyte apoptosis C = accumulation of D = fast repair of defectsB = fast bone loss unrepaired defects E = restoration of osteocytes

(Manolagas et al, 2000)

Treatment of GIO

• Primary prevention– Most rapid bone loss within 1st 6 – 12 months

of Rx

• Secondary prevention

Prevention of Glucocorticoid -induced bone loss

• Use lowest dose GC possible.

• Minimise lifestyle risk factors: quit smoking.

• Individualised exercise programmes.

• Drug Rx.

Drug treatment of osteoporosis

• Anti-resorptives:– Bisphosphonates– HRT/SERMS– Calcitonin

• Anabolics:– Teriparatide– Strontium ranelate

• Calcium & Vitamin D for all patients

GC doses ~ Prednisone >5mg/d for > 3 mo

Additional Risk Factors

·   Postmenopausal

·   Male > 50 y

·   Low weight

·   Prior fracture

·   High dose of prednisone (>10mg/day)

·   Underlying disease with rapid bone loss

. Immobilized due to underlying disease

. Low calcium intake

·  Family history of osteoporosis

CLINICALPRESENTATION

 BMD

 MANAGEMENT

(Sambrook PN)

Calcium and vitamin DRepeat BMD in 12 months if GC therapy ongoing.

T-scores ≥ –1.0

Therapy to prevent bone loss

First line:

Oral or IV bisphosphonates

Adjunctive or 2nd line therapy: Calcium and vitamin D

- 2.5 <T-scores

≤ –1.5

Consider

T-scores ≤ –2.5

Commence

Cost of treatment

• Bisphosphonates (alendronate): $280 per patient/year

• Individuals age 50+ using GC: ~ 1M (based on 10% of prevalence of using GC)

• Number of fractured cases reduced: 5240

• Treatment cost for prevention of one fracture: 53,579 USD

Summary

• Glucocorticoids widely used in clinical practice.

• >7.5mg/day Pednisone for >3-6 m of therapy, but no absolute cutoff below which GC treatment safe.

Summary

• Rapid bone loss (3-6 months) early prevention.

• Consideration for prevention:– fracture risk assessment – Effect of underlying disease – Effect of GC and other drugs on skeleton

• Bisphosphonates the mainstay of therapy.