advances in osteoporosis treatment
DESCRIPTION
Advances in osteoporosis treatment. John C Stevenson National Heart & Lung Institute Imperial College London Royal Brompton Hospital London, UK. PREVENTION & TREATMENT. anti-resorptive. bone formation. HRT tibolone SERMs bisphosphonates strontium calcitonin. teriparatide - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/1.jpg)
Advances in osteoporosis treatment
John C StevensonNational Heart & Lung Institute
Imperial College London
Royal Brompton Hospital
London, UK
![Page 2: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/2.jpg)
PREVENTION & TREATMENT
• HRT
• tibolone
• SERMs
• bisphosphonates
• strontium
• calcitonin
• teriparatide• ? strontium• ? HRT
anti-resorptive bone formation
![Page 3: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/3.jpg)
HRT RISKS
• breast cancer• inconclusive for E + P• no increase with E alone
• stroke• dose / route• no increase if HRT initiated below age 60 years
• venous thrombo-embolism• dose / route• transient increase seen with oral HRT• no increase with transdermal HRT
Stevenson et al. Atherosclerosis 2009; 207: 336-40
![Page 4: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/4.jpg)
BISPHOSPHONATES: RISKS
• gastro-intestinal side-effects
• atrial fibrillation• more severe with IV bisphosphonates
• osteonecrosis of the jaw• more common with IV bisphosphonates• follows dental extractions only
• inflammatory eye disease• only with IV bisphosphonates
• oesophageal cancer• only with oral bisphosphonates• taken for >3 years
• femoral stress fractures• long term bisphosphonates
Heckbert et al. Arch Intern Med 2008; 168: 826-31Seghizadeh et al. J Am Dent Assoc 2009; 140: 61-66Sharma et al. N Engl J Med 2008; 359: 1410-11
Green et al. BMJ 2010; 341: c4444Schilcher et al. N Engl J Med 2011; 364: 1728-37
![Page 5: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/5.jpg)
NEW TREATMENT APPROACHES
• target signalling systems to bone cells
• target cellular action of bone cells
![Page 6: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/6.jpg)
OSTEOCLAST REGULATION
TRAP cathepsin KRANK-L
M-CSF
PTH
1,25 (OH)2Destrogen
calcitonin
![Page 7: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/7.jpg)
OSTEOCLAST REGULATION
TRAP cathepsin KRANK-L
M-CSF
PTH
1,25 (OH)2Destrogen
calcitonin
![Page 8: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/8.jpg)
DENOSUMAB AND FRACTURES
• 7.868 osteoporotic women
• mean age 72.3 years
• randomised to denosumab 60 mg 6-monthly or placebo
• studied over median 3 years
• radiographic vertebral fracture HR 0.32 (CI 0.26-0.41)
• clinical hip fracture HR 0.60 (CI 0.37-0.97) 0
2
4
6
8
10
vertebral hip
% in
cide
nt f
ract
ures
p<0.001
Cummings et al. N Engl J Med 2009; 361: 756-65
denosumab
placebo
p<0.05
![Page 9: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/9.jpg)
OSTEOCLAST REGULATION
TRAP cathepsin KRANK-L
M-CSF
PTH
1,25 (OH)2Destrogen
calcitonin
![Page 10: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/10.jpg)
CATHEPSIN K INHIBITORS
• odanacatib (Merck)• 50 mg weekly• phase 3
• ONO-5334 (Ono)• 300 mg daily• phase 2
• MIV-711 (Medivir)• pre-clinical
![Page 11: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/11.jpg)
CATHEPSIN K INHIBITORS
0
1
2
3
4
5
6
spine hip
% B
MD
cha
nge
over
2 y
ears
0
1
2
3
4
5
6
spine hip
% B
MD
cha
nge
over
2 y
ears
odanacatib ONO-5334
Bone et al. J Bone Miner Res 2010; 25: 937-47 Eastell et al. J Bone Miner Res 2011; 26: 1303-12
![Page 12: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/12.jpg)
CATHEPSIN K INHIBITORS
• similar reduction in bone resorption markers to bisphosphonates
• lesser reduction in bone formation markers than with bisphosphonates
• rapid offset of action after stopping therapy
• skin adverse events seen with balicatib
• no serious adverse events seen with odanacatib or ONO-5334
Boonen et al. Curr Osteoporos Rep 2012; 10: 73-79
![Page 13: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/13.jpg)
![Page 14: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/14.jpg)
OSTEOBLAST REGULATION
PTH
Wnt/LRP
BMP
estrogen
cortisol
![Page 15: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/15.jpg)
OSTEOBLAST REGULATION
PTH
Wnt/LRP
BMP
estrogen
dkk
sclerostin
cortisol
![Page 16: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/16.jpg)
OSTEOBLAST REGULATION
PTH
Wnt/LRP
BMP
estrogen
dkk
sclerostin
cortisol
![Page 17: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/17.jpg)
SCLEROSTIN ANTIBODY AMG 785
-100
-50
0
50
100
150
200
% c
hang
e
P1NP BALPostecalcin CTX
0
1
2
3
4
5
6
% B
MD
cha
nge
spine hip
10 mg/kg SC
5 mg/kg IV
10 mg/kg SC
5 mg/kg IV
Padhi et al. J Bone Miner Res 2011; 26: 19-26
![Page 18: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/18.jpg)
FUTURE THERAPIES
• new bisphosphonates• zoledronate IV infusion annually (safety?)
• oestrogen + SERM• CEE + bazedoxifene
• cathepsin K inhibitors• odanacatib
• antibodies to sclerostin, dickkopf-1
• alternative administration of PTH• e.g. intranasal spray
![Page 19: Advances in osteoporosis treatment](https://reader035.vdocument.in/reader035/viewer/2022062410/568158f9550346895dc63533/html5/thumbnails/19.jpg)
CONCLUSIONS
• various treatment options are available, but all carry risks
• HRT remains treatment of choice for prevention in women
• new treatments are being developed from our better understanding of bone physiology
• targeting cell signalling systems may affect tissues other then bone