OSTEOPOROSIS and fracture risk

Prof. J. Preželj

KO za endokrinologijo, diabetes in presnovne bolezni

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

normal bone turnover

• cleansing

• quiescence

• formation

osteoidmineralisation

• resorption

• quiescence

interleukins

resorption products

RANKL & OPG

“COUPLING”

osteoblast

osteoclast

RANK/RANKL/OPG SYSTEM

preosteoclast

preosteoblast

osteoblastosteoclast

Physiological control of resorption/formation balance

(hormones, factors):

PTH, PTHrP, GK, TNF, Il-1,6,11,

17, PGE2…

“up” or “down” regulation of expresion

“bone quantity” (BMD)

“bone quality”• turnover• collagen structure• microarchitecture• etc.

bone strenght

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.

AGEMENOPAUSE

70 years

MOST FREQUENT OSTEOPOROTIC FRACTURES

bone strenghtBMD quality

≈ ≈≈ fracture risk: NORMAL

fracture risk: INCREASED

fracture risk: INCREASED

fracture risk: VERY HIGH

bone strenghtBMD quality

≈

bone strenghtBMD quality

bone strenghtBMD quality

≈

bone strenghtBMD quality

… data validated through extensive epidemiological research:

age sex weight height previous fracture parent fracture hip

current smokingsecondary osteoporosis

alcohol > 3 units per day

glucocorticoids

rheumatoid arthritis

Ten year fracture probability (%)

Indirect estimate of quality through ..

Computerbased

algorithmFRAXDXA

scan

BMD (T – score)

T> -1,0

-1,0 > T > -2.5

T < -2,5

normal

osteopenia

osteoporosis

result

(femoral neck BMD)

Postmenopausal women I. previous fragility fracture(s) of vertebrae or hip

exclusion of 2nd osteoporosis Th

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

Age (years) T - score

FRAXTM III. fracture risk > 20/5 % Th

preventive measures fracture risk < 20/5 %

Guidelines for starting therapy in high risk patients

exclusion of 2nd osteoporosis Th

!!!Če T < - 2.5 “laboratory is obligatory”

S - Ca, S - A. PHOSPHATASE SR (U - proteins, S - proteinogram) S - creatinin, S - urea S - AST (GOT), S - ALT (GPT), S - gama GT hemogram S - P S - TSH

Therapy (reducing fracture risk)

Lifestyle changes

Calcium and vitamin D

Drugs

1 dl milk ≈ 120 mg Ca100 g cheese ≈ 1000 mg Ca100 g curd cheese ≈70 mg Ca

Others:women ≈ 250 mgmen ≈ 350 mg

1 g CaCO3 ≈ 400 mg Ca1 g Ca citrate ≈ 240 mg Ca1 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)

ANTIRESORPTIVES

ANABOLICS

COMBINED ACTIONfo

rmat

ion

resorption

Calcium and vitamin D

Drugs

Lifestyle changes

Therapy (reducing fracture risk)

DRUG DOSE APPLICATION

EVISTA (raloksifen) 60 mg tbl/d p/o

FOSAVANCE 5600 (alendronate + vitD3)

70 mg tbl/week p/o

75 mg tbl/2 consecutive days/month p/oACTONEL 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 months i.v.

ACLASTA (zoledronic acid 5 mg in 100 ml/ year i.v.

PROLIA (denosumab) 60 mg / 6 months s.c.

PROTELOS (strontium ranelate) 2 g granula/d p.o.

FORSTEO (teriparatide) 20 μg /d s.c.

AN

TIR

ES

OR

PT

IVE

S

COMBINED ACTION

ANABOLIC

Drugs for reducing fracture risk

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.

reimbursement

comorbidity

patient expectations

bisphosphonates

raloxifene

HRT

PTH

Sr ranelate

hip fracture

risk

age

deno

sumab

QUESTIONS ?