藥劑科實習生:黃中成指導老師:蘇蜂琪藥師

2014.08.13

Osteoporosis

Outline

Epidemiology

Definitions

Classification

Other risk factors Associated With Development of Osteoporosis Classification

Clinical Presentation

Diagnosis

Bone remodeling model

Pharmacologic Therapy

Non-pharmacologic therapy

Conclusion

EpidemiologyThe rapid increase in the global population of osteoporosis

http://bone.la-dy.net/wiki/img_auth.php/6/68/072506.jpg

Definitions★

Osteoporosis is a bone disorder characterized by

low bone density , impaired bone architecture, and compromised bone strength predisposing a person to increased fracture risk.

Normal Osteoporosis

Classification★Primary Osteoporosis:․Postmenopausal Osteoporosis:

Estrogen deficiency during menopause increasesactivation of new osteoclasts to lose bone mass .

․Age-Related Osteoporosis:

Because of PTH , calcium , and vitamin D deficiencies leading to accelerated bone turnover andreduced osteoblast formation.

Classification★Secondary Causes of Osteoporosis:‧Cushing syndrome

‧Hyperthyroidism

‧Primary hyperparathyroidism

‧Gastrointestinal disease

‧Drugs:․corticosteroids

․long-term anticonvulsant therapy

․Loop diuretics

Other risk factors Associated With development of Osteoporosis‧Asian

‧Small stature or Low Weight

‧Excessive alcohol intake or Cigarette smoking

‧ Early menopause or oophorectomy

Clinical Presentation

Fracture(Spine、Hip、Wrist or Colles’ )

Back pain

Low activity

Kyphosis or Lordosis

Decrease height

Spine

Hip

Wrist or Colles’

Diagnosis

A WHO working group defined osteoporosis as the presence of bone mineral density(BMD) or a T-score.

Measurement of central(hip and spine)BMD with dual-energy X-ray absorptiometry(DXA) is the gold standard for osteoporosis diagnosis.

DiagnosisT-score(SD)

Bone density

Normal Bone Mass

Osteopenia

Osteoporosis

Bone remodeling model

‧Stimulating factor:‧PTH(intermittent)‧1,25(OH)2D3‧ T3 / T4‧TGF-β

‧Inhibiting factor:‧Glucocorticoid

teriparatide

Inhibiting factor:PTH(continuous)

EstogenRaloxifen

e

DenosumabBisphosphates

strontiu m

ranelate

Calcitonin

TGF-β

Cathepsin Kinhibitor

Osteoprotegerin(OPG)

1,25(OH)2D3High dose

Antiresorptive agents

Anabolic agents

Pharmacologic therapy★Bisphosphonates:

Bisphosphonateshydroxyapatite

Osteoclast

combination

Apoptosis

Pharmacological mechanism of Bisphosphonates

http://en.wikipedia.org/wiki/File:BisphosStruct.svg

Alendronate Risedronate Ibandronate Zoledronic acid Dosing 70mg Orally

once weekly150mg Orally once monthly

3mg IV infused over no less than 15 minutes. (once every 3 months)

5mg IV infused over no less than 15 minutes. (once every 12 months)

AdverseEffects

‧Esophagitis‧ONJ‧musculoskeletal

pain

‧Esophagitis‧ONJ‧musculoskeletal

pain

‧headache ‧arthralgiamusculoskeletal pain

‧Fevers ‧flulike‧symptoms ‧headache ‧arthralgia ‧musculoskeletal

pain

Pharmacologic therapySERMs:

Raloxifene

RANKL inhibitor :

Denosumab

PTH:

teriparatidestrontium ranelate

Dosing 60 mg orally once daily

60 mg subcutaneous once every 6 months

20 mcg subcutaneously once daily for up to 2 years.

2 gm Granules orally once daily

Adverse Effects ‧venous thromboembolic disease(VTE)

‧ONJ‧serum Ca ↓‧Back pain

‧Dizzy ‧Cramp ‧Diarrhea

‧Headache ‧vomiting ‧Diarrhea ‧GI disease ‧VTE‧DRESS,SJS,TEN

Contraindications Congestive heart failure

Low serum Ca Osteosarcoma:‧Paget bone

disease ‧unexplained

alkalinephosphataseelevations

‧open epiphyses

‧transient ischemic attacks‧Antacid with

cation ion ‧tetracycline ‧quinolone

Therapy of osteoporosis in men:Drugs Form of Drugs

Alendronate(Fosamax®)

Oral(tablet)Oral(liquid solution)

Alendronate(Fosamax® Plus Vit D)

Oral(tablet)

Risedronate(Actonel®)

Oral(tablet)

Parathyroid Hormone(teriparatide / Ferteo®)

Injection(IM‚SC)

strontium ranelate(Protos®)

Oral

Therapy of Postmenopausal Osteoporosis:Drugs Form of Drug

Alendronate(Fosamax®)

Oral(tablet)Oral(liquid solution)

Alendronate(Fosamax® Plus Vit D) Oral(tablet)Ibandronate(Boniva®)

Oral(tablet)Intravenous(IV)

Risedronate(Actonel®)

Oral(tablet)

Zoledronic acid(Reclast®，Taiwan called Aclasta®)

Intravenous(IV)

SERMsRaloxifene(Evista®) Oral(tablet)

Human monoclonal antibody for RANKL:

Denosumab(Prolia®)

Injection(SC)

Parathyroid Hormone(teriparatide / Ferteo®)

strontium ranelate(Protos®)

Injection(IM‚SC)

Oral

Non-pharmacologic therapy: Vitamin D 、PTH and Calcium

PTH

25-hydroxyvitamine D

1,25-dihydroxyvitamine D

Ca resorption

Decrease resorption of P

TH

Ca resorption

Glucocorticoids

Increase excretion of Ca

Blood —Low CalciumConcentration

Calciumfor Resorption

Conclusion:★目前骨質疏鬆症治療的首選藥為雙磷酸鹽類，尤以口服劑

型為優先。至於藥物合併使用方面，一般不建議併用二種抗 溶蝕藥品，如雙磷酸鹽類加Raloxifene的治療，因其會過度

抑制骨骼汰舊率，導致骨骼太脆。而Alendronte合併 teriparatide對骨質密度無好處，且會降低teriparatide的同化

效果。★想要維持良好的骨健康，從年輕時期就應養成良好生活型

態，避免煙、酒和過量咖啡，均衡營養和規律運動，並多補 充鈣質，儲存骨本，使身體有較高的｢尖峰骨量｣。

★中年時期更須加強保護骨本，更年期婦女應儘早評估是否 宜補充女性荷爾蒙預防骨流失;年老時期則須加強防跌以防

範生骨折。

Reference

MICROMEDEX

APPLIED THERAPEUYICS TENTH EDITION

藥學雜誌 119版 69-74 骨質疏鬆症的治療

Airiti 骨質疏鬆症的藥物治療

行政院衛生署國民健康局-骨質疏鬆症-臨床治療指引

臺安醫院

醫藥專欄

http://mypaper.pchome.com.tw/an8100shaow/post/13253484 07

http://www.nhsdirect.wales.nhs.uk/encyclopaedia/c/article/co rticosteroid(drugs)

http://www.scoopthelake.com/2014/04/29/risk-factors- osteoporosis-women/

http://www.ultimatechirocare.com/cat-news-healthcare- naperville-woodridge-lisle-illinois-il/what-are-the-symptoms- of-osteoporosis/

http://healthyliving88.com/osteoporosis/treatment-care/

http://mypaper.pchome.com.tw/an8100shaow/post/1325348407http://mypaper.pchome.com.tw/an8100shaow/post/1325348407http://www.nhsdirect.wales.nhs.uk/encyclopaedia/c/article/corticosteroid(drugs)http://www.nhsdirect.wales.nhs.uk/encyclopaedia/c/article/corticosteroid(drugs)http://www.scoopthelake.com/2014/04/29/risk-factors-osteoporosis-women/http://www.scoopthelake.com/2014/04/29/risk-factors-osteoporosis-women/http://www.ultimatechirocare.com/cat-news-healthcare-naperville-woodridge-lisle-illinois-il/what-are-the-symptoms-of-osteoporosis/http://www.ultimatechirocare.com/cat-news-healthcare-naperville-woodridge-lisle-illinois-il/what-are-the-symptoms-of-osteoporosis/http://www.ultimatechirocare.com/cat-news-healthcare-naperville-woodridge-lisle-illinois-il/what-are-the-symptoms-of-osteoporosis/

OsteoporosisOutline�Epidemiology�DefinitionsClassificationClassificationOther risk factors Associated With development of OsteoporosisClinical PresentationDiagnosisDiagnosis�Bone remodeling model投影片編號 12Pharmacologic therapy投影片編號 14Pharmacologic therapyTherapy of osteoporosis in men:Therapy of Postmenopausal Osteoporosis:Non-pharmacologic therapy:�Vitamin D 、PTH and CalciumConclusion:Reference投影片編號 21