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

2. Epidemiology of GIO Prevalence of oral glucocorticoid use ~1% of the adult population 1 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)

3. GC in developing countries Prevalence: unknown. Glucocorticoid can be purchased over the counter.

4. Projected number of glucocorticoid use among 50+ Prevalence of using glucocorticoid Number of individuals using glucocorticoid (x1000)

5. Mechanism of Corticosteroid Induced Osteoporosis (Segal L G et al. 1997) D1202 Osteoporosis Osteoblast bone formation PTH? Effects on growth hormones & growth factors gastrointestinal calcium absorption urinary calcium excretion calcium Corticosteroids osteoclast bone resorption Sex hormone effects: adrenal androgens oestrogen testosterone muscle mass

6. * * * * p <0.01 vs. baseline Effect of steroids on bone mineral density % Bone change vs baseline ( Mulder H et al. 1994) D1202 Months

7. 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.

8. Fracture type and the use of Glucocorticoid Fracture typeGenderCorticosteroid use Prior fracture Any fractureM1.7 (1.1–2.5)1.7 (1.4–2.1 ) F1.4 (1.2–1.6)1.7 (1.6–1.9) Osteoporotic fracture M2.2 (1.4–3.3)1.7 (1.4–2.1) F1.4 (1.2–1.7)1.7 (1.6–1.9) Hip fractureM2.6 (0.9–7.5)1.7 (1.0–2.9) F2.1 (1.4–3.1)1.7 (1.3–2.1) (Kanis JA, et al, 2004)

9. Projected number of GC-induced fractures per year for men and women aged 50+ Prevalence of using glucocorticoid Any fractureHip fracture

10. Incidence of non-vertebral fractures (per 100 p-yrs) in women (van Staa et al, 2000) 0 1 2 3 4 5 6 7 8 Control < 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 users 244.235 controls 58.6% female

11. Incidence of non-vertebral fracture before, during and after steroid therapy 24 1 6 60 3 30 van Staa JBMR 2000

12. 3 to 6 months Time 3 to 6 months Bone Strength Steroid therapy A + B CD + E A = osteocyte apoptosisC = accumulation ofD = fast repair of defects B = fast bone loss unrepaired defectsE = restoration of osteocytes (Manolagas et al, 2000)

13. Treatment of GIO Primary prevention –Most rapid bone loss within 1 st 6 – 12 months of Rx Secondary prevention

14. Prevention of Glucocorticoid -induced bone loss Use lowest dose GC possible. Minimise lifestyle risk factors: quit smoking. Individualised exercise programmes. Drug Rx.

15. Drug treatment of osteoporosis Anti-resorptives: –Bisphosphonates –HRT/SERMS –Calcitonin Anabolics: –Teriparatide –Strontium ranelate Calcium & Vitamin D for all patients

17. 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 CLINICAL PRESENTATION BMD MANAGEMENT (Sambrook PN) Calcium and vitamin D Repeat 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

18. 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

19. 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.

20. 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.