1040703骨質疏鬆治療

Optimizing osteoporosis care the Roles of FOSAMAX PLUS 5600 and the Importance of Vitamin D

(Rickets) ) 17

D 1919 rickets animal model, dogs feeding with bread and low-fat milk Ineffective by adding yeast (provide vitamin B) adding orange juice (provide vitamin C)

Effective by addition of butterfat and cod-liver oil 1920 Hopkins

fat-soluble factor A (

A)

1922 McCollum observed that heated, oxidized cod-liver oil could not prevent xerophthalmia but could cure rickets in the rats ( D)

D UVB

Ergosterol

7-dehydrocholesterol

Calciferol (vitamin D2)

Cholecalciferol (vitamin D3)

D Sun

U VB

ProD3 PreD3 Vitamin D3

小腸

皮膚

Diet Vitamin D3 Vitamin D2

肝臟 25(OH)D (inactive form

腎臟 小腸 PTH (+)

1,25(OH)2D (active form

(+) Low PO42–

)

25(OH)D=25-hydroxyvitamin D; 1,25(OH)2D=1,25-dihydroxyvitamin D Adapted from Holick MF Osteoporos Int 1998;8(suppl 2):S24–S29.

)

D • 25OHD • long circulating half-life of 15 days • reflects vitamin D produced in the skin as well as that acquired from the diet

• 1,25(OH)2D • short half-life of 15 hours • tightly regulated by parathyroid hormone, calcium, and phosphate, such that it does not decrease significantly until vitamin D deficiency is already well advanced

The serum 25OHD concentration is the best available clinical indicator of vitamin D status

1–4

Definition of 25(OH)D Levels

Inadequacy Deficiency

Insufficiency

Optimal

Serum 25(OH)D, ng/mL 0

10

20

30

40

0

25

50

75

100

Serum 25(OH)D, nmol/L

Serum concentration of 25(OH)D, the main circulating metabolite of vitamin D, is the correct functional indicator of vitamin D status.

Serum 1,25(OH)2D should not be measured routinely, as it is not reflective of vitamin D status.

Vitamin D deficiency <9 ng/mL; vitamin D inadequacy <30 ng/mL 1. Binkley N et al. Endocrinol Metab Clin N Am. 2010;39(2):287–301; 2. Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press; 1997; 3. Friedman PA. In: Brunton LL et al, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill Medical Publishing Division; 2006: 1647–1678; 4. Bikle DD et al. J Clin Endocrinol Metab. 1985;61(5):969–975.

Mechanism of Action: Vitamin D and Bone Metabolism

1–4

Balanced System

Low Levels of Vitamin D

Calcium absorption meets metabolic demands Normal bone mineralization is maintained

Calcium reservoir of bone is depleted to correct for low calcium absorption in gut

Dietary calcium

4

Mobilization of calcium from bone

Gut

1 Vitamin D

Circulation Vitamin D

In vitamin D– deficient state, calcium absorption decreases

2

3

PTH Parathyroid Low calcium causes increase in PTH secretion

Calcium reabsorption

PTH

Renal distal tubule

PTH=parathyroid hormone.

1. Holick MF. Curr Opin Endocrinol Diabetes. 2002;9:87–98; 2. DeLuca HF. Am J Clin Nutr. 2004;80(suppl 1):1689S–1696S; 3. Lips P. Endocr Rev. 2001;22(4):477–501; 4. Holick MF. J Nutr. 2005;135:2739S–2748S.

•The rationale of vit D supplementation •The efficacy of vit D supplementation •How to do it in daily practice

D In a cross-sectional, observational, international study in 2589 postmenopausal women with osteoporosis 90

81.8%

N=2589

Prevalence (%)

80 70

71.4%

63.9%

60

53.4%

57.7%

Latin America 拉丁美洲

Europe 歐洲

60.3%

50 40 30 20 10 0

All 全球

Middle East 中東

Regions

Asia 亞洲

Australia 澳洲

韓國,日本,馬來西亞,泰國

*Vitamin D inadequacy was defined as serum 25(OH)D <30 ng/ml Study Design: Observational, cross-sectional study of 2589 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D distribution.

Adapted from Lips P et al. Poster presented at ASBMR, Nashville, TN, USA, September 23–27, 2005; Heaney RP Osteoporos Int 2000;11:553–555.

D

Prevalence (%)

N=548

100 90 80 70 60 50 40 30 20 10 0

98.0% 98.9% 92.7% 95.6% 81.0%

68.4%

n Patients >60 years old

hospitalized for nontraumatic fractures n Serum 25(OH)D < 30 ng/ml

in 97.8% n Patients had no vitamin D

supplementation <12

<16

<20

<24

<28

<32

Cutoff points for 25(OH)D concentration (ng/ml) *Vitamin D inadequacy was defined as serum 25(OH)D <30 ng/ml Study Design: Multicenter study of 548 patients in Scotland aged >60 years who were hospitalized with hip fractures to assess the prevalence of vitamin D inadequacy (measured by serum 25[OH]D).

Adapted from Gallacher SJ et al Curr Med Res Opin 2005;21:1355â&#x20AC;&#x201C;1361; Heaney RP Osteoporos Int 2000;11:553â&#x20AC;&#x201C;555.

Slide 12

Vit D status and response to treatment in postmenopause osteoporosis Osteoporos Int. 2009 Feb;20(2):239-44.

•The rationale of vit D supplementation •The efficacy of vit D supplementation •How to do it in daily practice

â&#x20AC;&#x153;The treatment effect was also best with calcium doses of 1200 mg or more, or vitamin D doses of 800 IU or more

NOF Update its Recommendations for Calcium and Vitamin D3 Intake in 2007!!

800 - 1,000 I.U. of vitamin D3/day for adults 50 and older

1200 mg of calcium/day for adults 50 and older

National Osteoporosis Foundation March 13, 2007

•The rationale of vit D supplementation •The efficacy of vit D supplementation •How to do it in daily practice

D • • • • • • • •

D

100

8~60 200~800 140~150 8500 10 60000 40 28

D

I.U.

D

D

• Sun Protection Factor SPF • SPF15 15 14

UVB UVB

15

sunscreen with an SPF 15 can reduce synthetic capacity by 98% Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium (2011)

D Aspray TJ, Bowring C, Fraser W, et al: National osteoporosis society vitamin D guideline summary. Age and Ageing 2014; 43: 592â&#x20AC;&#x201C;5.

•

25OHD

•

D

•

D vitamin D3

D hyperparathyroidism

•

25OHD

25OHD • 25OHD<30nmol/l

vitamin D deficiency

• 25OHD

vitamin D insufficiency

30 50nmol/l

• 25OHD 50nmol/l

normal

1–4

Definition of 25(OH)D Levels

Inadequacy Deficiency

Insufficiency

Optimal

Serum 25(OH)D, ng/mL 0

10

20

30

40

0

25

50

75

100

Serum 25(OH)D, nmol/L

Serum concentration of 25(OH)D, the main circulating metabolite of vitamin D, is the correct functional indicator of vitamin D status.

Serum 1,25(OH)2D should not be measured routinely, as it is not reflective of vitamin D status.

Vitamin D deficiency <9 ng/mL; vitamin D inadequacy <30 ng/mL 1. Binkley N et al. Endocrinol Metab Clin N Am. 2010;39(2):287–301; 2. Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press; 1997; 3. Friedman PA. In: Brunton LL et al, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill Medical Publishing Division; 2006: 1647–1678; 4. Bikle DD et al. J Clin Endocrinol Metab. 1985;61(5):969–975.

D 800

( 40 IU

2000IU

g)

100IU vitamin D3

D D 1 g vitamin D3

IU

25OHD level 0.7 ~ 1.1 ng/ml

Vitamin D Supplements in Taiwan: D 400 IU

D

D

GN嚼

$650

(60 t瑞生美ets)

400 IU

$490 (100 t瑞生美ets)

400 IU

$360 (60 t瑞生美ets)

400 IU

$469 (60 t瑞生美ets) $645

Main Concerns : Bisphosphonates •

Osteonecrosis of jaw (ONJ)

•

Gastrointestinal irritation

•

Flu-like syndrome

Main Concerns : Bisphosphonates •

Osteonecrosis of jaw (ONJ)

•

Gastrointestinal irritation

•

Flu-like syndrome

An Open -Label Open-Label Clinical Study of Alendronate Plus Colecalciferol

FOCUS D Open-Label Study

Patients With Low Vitamin D Levels: 25(OH)D <20 ng/mL1,2 Baseline Week 26 Week 52

100 84.2

84.0

Patients, %

80 60 40 20 0

36.9

31.0

(n=257)

8.6a

11.3a

(n=221)

(n=212)

Alendronate 70 mg + Colecalciferol 5600 IU

(n=258)

(n=216)

(n=203)

Referred Care

• Significantly fewer patients with low vitamin D levels with alendronate + colecalciferol FOCUS D=FOsavance vs Standard Care – Use and Study of Vitamin D. aP<0.001 vs referred care at each time point.

1. Ralston SH et al. Calcif Tissue Int. 2011 Apr 11. [Epub ahead of print.]; 2. Reginster YV et al. Poster presented at: European Congress on Osteoporosis and Osteoarthritis; 23–26 March 2011; Valencia, Spain.

FOCUS D Open-Label Study

BMD Changes From Baseline at 12 Months1,2 Alendronate 70 mg + colecalciferol 5600 IU Referred care

LS Mean (95% CI) BMD Change From Baseline, %

8 6

Treatment Difference: 1.01 (P=0.047) 4.92 3.91

4

Treatment Difference: 0.82 (P=0.035) 2.22 1.40

2 0 (n=226)

(n=219)

Lumbar Spine

(n=227)

(n=218)

Total Hip

FOCUS D=FOsavance vs Standard Care â&#x20AC;&#x201C; Use and Study of Vitamin D; BMD=bone mineral density; LS=least square; CI=confidence interval.

1. Ralston SH et al. Calcif Tissue Int. 2011 Apr 11. [Epub ahead of print.]; 2. Reginster YV et al. Poster presented at: European Congress on Osteoporosis and Osteoarthritis; 23â&#x20AC;&#x201C;26 March 2011; Valencia, Spain.

Thanks for your attention !!