1040703骨質疏鬆治療 by ksdoctor

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 (

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

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

Mobilization of calcium from bone

Gut

1 Vitamin D

Circulation Vitamin D

In vitamin D– deficient state, calcium absorption decreases

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%

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.

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 • • • • • • • •

100

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

I.U.

• Sun Protection Factor SPF • SPF15 15 14

UVB UVB

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 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

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.

D 800

( 40 IU

2000IU

100IU vitamin D3

D D 1 g vitamin D3

25OHD level 0.7 ~ 1.1 ng/ml

Vitamin D Supplements in Taiwan: D 400 IU

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

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 !!