1. OSTEOPOROSIS and fracture risk Prof. J. Preželj KO za endokrinologijo, diabetes in presnovne bolezni

2. extracellular matrix: bone architecture: trabeculae bone cells: organic – colagen typ 1 (osteocalcin, osteopontin etc) 30 % 70 % osteoblasts osteoclasts osteocytes Composition of bone anorganic (Ca, P) – hydroxy apatite

3. normal bone turnover cleansingcleansing quiescencequiescence formationformation osteoid mineralisation resorptionresorption quiescencequiescence

4. interleukins resorption products RANKL & OPG “COUPLING” osteoblast osteoclast

5. RANK/RANKL/OPG SYSTEM preosteoclast preosteoblast osteoblast osteoclast Physiological control of resorption/formation balance (hormones, factors): PTH, PTHrP, GK, TNF, Il-1,6,11, 17, PGE2… “up” or “down” regulation of expresion

6. “bone quantity” (BMD) (BMD) “bone quality” “bone quality” turnover turnover collagen structure collagen structure microarchitecture microarchitecture etc. etc. bone strenght

7. Osteoporosis is a skeletal disease… …characterized by low bone mass and and micro architecural deterioration of bone tissue with a consenquent INCREASE IN BONE FRAGILITY (bone strenght is reduced) and susceptibility to FRACTURE.

8. AGEMENOPAUSE 70 years MOST FREQUENT OSTEOPOROTIC FRACTURES

9. bone strenght BMD quality ≈ ≈≈ fracture risk: NORMAL INCREASED INCREASED VERY HIGH bone strenght BMD quality ≈ BMD quality BMD quality ≈

10. BMD quality … data validated through extensive epidemiological research: age sex weightheight previous fracture parent fracture hip current smoking secondary osteoporosis alcohol > 3 units per day glucocorticoids rheumatoid arthritis Ten year fracture probability (%) Indirect estimate of quality through.. ComputerbasedalgorithmFRAX DXA scan BMD (T – score) T> -1,0 -1,0 > T > -2.5 T < -2,5 normal osteopenia osteoporosis result (femoral neck BMD)

11. Postmenopausal women I. previous fragility fracture(s) of vertebrae or hip I. previous fragility fracture(s) of vertebrae or hip exclusion of 2 nd osteoporosis Th combination of age and T score < -2.5 (over L1-L4 and/or neck and/or total hip) II. combination of age and T score < -2.5 (over L1-L4 and/or neck and/or total hip) - 0.5 - 1.0 - 1.5 - 2.0 - 2.5 - 3.0 - 3.5 - 4.0 - 4.5 50 - 59 60 - 64 65 - 70 > 70 > 70 Age ( years ) T - score FRAX TM III. fracture risk > 20/5 % Th preventive measures fracture risk < 20/5 % fracture risk < 20/5 % Guidelines for starting therapy in high risk patients exclusion of 2 nd osteoporosis Th

12. !!! Če T < - 2.5 “laboratory is obligatory” S - Ca,  S - Ca,  S - A. PHOSPHATASE SR (U - proteins, S - proteinogram)  SR (U - proteins, S - proteinogram)  S - creatinin, S - urea  S - AST (GOT), S - ALT (GPT), S - gama GT  hemogram  S - P  S - TSH

13. Therapy (reducing fracture risk) Lifestyle changes Calcium and vitamin D Drugs

14. 1 dl milk ≈ 120 mg Ca 100 g cheese ≈ 1000 mg Ca 100 g curd cheese ≈70 mg Ca Others: women ≈ 250 mg men ≈ 350 mg 1 g CaCO3 ≈ 400 mg Ca 1 g Ca citrate ≈ 240 mg Ca 1 g Ca lactogluconate ≈ 90 mg Ca Ca in foods Ca supplements += 1200 mg Ca Calcium and vitamin D Drugs Lifestyle changes Therapy (reducing fracture risk)

15. ANTIRESORPTIVES ANABOLICS COMBINED ACTION formationresorption Calcium and vitamin D Drugs Lifestyle changes Therapy (reducing fracture risk)

16. DRUG DOSE APPLICATION EVISTA (raloksifen) 60 mg tbl/dp/o FOSAVANCE 5600 (alendronate + vitD3) 70 mg tbl/weekp/o 75 mg tbl/2 consecutive days/monthp/o ACTONEL 75 MG (risedronate) ACTONEL COMBI 75 MG (risedronat + 1000 Mg Ca + 880 IU vit D) 35 mg tbl/ week + (Ca + vit D) granula/d p/o BONVIVA (ibandronate) 150 mg tbl/month p/o BONVIVA IV (ibandronaet) 3 mg in 3 ml/ 3 monthsi.v. 3 mg in 3 ml/ 3 monthsi.v. ACLASTA (zoledronic acid 5 mg in 100 ml/ yeari.v. 5 mg in 100 ml/ yeari.v. PROLIA (denosumab) 60 mg / 6 monthss.c. 60 mg / 6 monthss.c. PROTELOS (strontium ranelate) 2 g granula/dp.o. 2 g granula/dp.o. FORSTEO (teriparatide) 20 μg /ds.c. 20 μg /ds.c. ANTIRESORPTIVES COMBINED ACTION ANABOLIC Drugs for reducing fracture risk

17. How to prescribe antiosteoporotic therapy? AMERICAN COLLEGE OF PHYSICIANS We recommend that the choice of therapy be guided by judgment of the risks, benefits, and adverse effects of drug options for each individual patient. We recommend that the choice of therapy be guided by judgment of the risks, benefits, and adverse effects of drug options for each individual patient. reimbursementcomorbidity patient expectations bisphosphonates raloxifene HRT PTH Sr ranelate hip fracture risk age denosumab

18. QUESTIONS ?