Fall prevention with supplemental and active forms of vitamin D

Fall prevention with supplemental and active forms of vitamin D

Bischof-Ferrari BMJ 2009;339:b3692

Cochrane Database Syst Rev 2010(1):CD005465

Cochrane review 2010

Cochrane Database Syst Rev 2010(1):CD005465

Cochrane review 2010

post-hoc subgroup < 50 nmol/l 25(OH)D :

• rate of falls levels (RR 0.57, 95% CI 0.37 to 0.89) in 260 participants, 2 trials

J Am Geriatr Soc 2010, 58(7):1299-1310

J Am Geriatr Soc 2010, 58(7):1299-1310

fall reduction was significant in several subgroups of individuals: 1.mean age younger than 802.additional calcium therapy3.dose of 800 IU or greater4.cholecalciferol therapy

no evidence was found of a relation between higher doses of vitamin D or longer duration of vitamin D therapy and treatment effect

Calcium en vitamine D in interventie trials

2005-2010: 7 Meta-analyses vitamine D en fractuurreductie

• Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B: Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005, 293(18):2257-2264.

• Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P: Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab 2007, 92(4):1415-1423.

• Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A: Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007, 370(9588):657-666.

• Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J: Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 2009, 169(6):551-561.

• Avenell A, Gillespie WJ, Gillespie LD, O'Connell D: Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2009(2):CD000227.

• Bergman GJ, Fan T, McFetridge JT, Sen SS: Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: a meta-analysis. Curr Med Res Opin 2010, 26(5):1193-1201.

• Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 2010, 340:b5463

van den Bergh, Curr osteoporos reviews, in press

Bischoff-Ferrari. JAMA 2005, 293(18):2257-2264.Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.

• 5 RCTs for hip fracture (n = 9294)

• 7 RCTs for nonvertebral fracture risk (n = 9820)

• vitamin D 700 to 800 IU/d reduced the relative risk of hip fracture by 26% (3 RCTs with 5572 persons; RR 95% CI 0.61-0.88)

• any nonvertebral fracture by 23% (5 RCTs with 6098 persons; RR 95% CI, 0.68-0.87) versus calcium or placebo in individuals ≥60 years

• No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons)

Bischoff-Ferrari. JAMA 2005, 293(18):2257-2264.Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.

• 5 RCTs for hip fracture (n = 9294)

• 7 RCTs for nonvertebral fracture risk (n = 9820)

• vitamin D 700 to 800 IU/d colecalciferol reduced the relative risk of hip fracture by 26% (3 RCTs with 5572 persons; RR 95% CI 0.61-0.88)

• any nonvertebral fracture by 23% (5 RCTs with 6098 persons; RR 95% CI, 0.68-0.87) versus calcium or placebo in individuals ≥60 years

• No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons)

• => 700-800 IU/d vitamin D3

Boonen S. J Clin Endocrinol Metab 2007, 92(4):1415-1423.Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative meta-analysis of randomized controlled trials.

• designed to extend the findings of Bischoff-Ferrari et al. 2005

• A total of 53,260 patients from nine RCTs were included in this analysis and all RCTs used cholecalciferol with a dose of 700–800 IU/d in six trials and 400 IU/d in the other three trials.

• Calcium (500–1200 mg/d) was given with vitamin D in six RCTs.

• only vitamin D with additional calcium demonstrated a significant reduction of hip and nonvertebral fractures versus placebo or no treatment

• It has to be noted that two trials with very low nutritional baseline calcium intake had an important impact on the results of this meta-analysis

Boonen S. J Clin Endocrinol Metab 2007, 92(4):1415-1423.Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative meta-analysis of randomized controlled trials.

• designed to extend the findings of Bischoff-Ferrari et al. 2005

• A total of 53,260 patients from nine RCTs were included in this analysis and all RCTs used cholecalciferol with a dose of 700–800 IU/d in six trials and 400 IU/d in the other three trials.

• Calcium (500–1200 mg/d) was given with vitamin D in six RCTs.

• only vitamin D with additional calcium demonstrated a significant reduction of hip and nonvertebral fractures versus placebo or no treatment

• It has to be noted that two trials with very low nutritional baseline calcium intake had an important impact on the results of this meta-analysis

• => + calcium, low nutritional intake

Tang. Lancet 2007, 370(9588):657-666.Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis.

• 17 trials met 63.897 personen: (RR 0.88; CI 0.83-0.95, p=0.0004)

• 1000 mg per dag calcium monotherapie in 6 van de 9 trials: RR 0.90 (CI 0.80-1.00)

• 7 van de 8 trials met calcium in combinatie met vitamin D:RR 0.87 (0.77-0.97), waarin beide analyse niet significant van elkaar verschilden.

• 25(OH)D3 <25 nmol/l: met calcium en vitamine D-suppletie een grotere risicoreductie dan met calcium monotherapie (RR 0.86 vs. 0.94; p=0.06)

• Dit effect verdween bij een afkappunt voor serum 25(OH)D van 50 nmol/l

• Het effect was groter bij mensen met een lage calciuminname via de voeding (<700 mg/dag) en bij calciumdoseringen van 1200 mg

Tang. Lancet 2007, 370(9588):657-666.Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis.

• 17 trials met 63.897 patienten individuen: (RR 0.88; CI 0.83-0.95, p=0.0004)

• 1000 mg per dag calcium monotherapie in 6 van de 9 trials: RR 0.90 (CI 0.80-1.00)

• 7 van de 8 trials met calcium in combinatie met vitamin D:RR 0.87 (0.77-0.97), waarin beide analyse niet significant van elkaar verschilden.

• 25(OH)D3 <25 nmol/l: met calcium en vitamine D-suppletie een grotere risicoreductie dan met calcium monotherapie (RR 0.86 vs. 0.94; p=0.06)

• Dit effect verdween bij een afkappunt voor serum 25(OH)D van 50 nmol/l

• Het effect was groter bij mensen met een lage calciuminname via de voeding (<700 mg/dag) en bij calciumdoseringen van 1200 mg

• => combinatie van calcium en vitamine D bij lage calciuminname en bij 25(OH)D<50 nmol/l)

Bischoff-Ferrari. Arch Intern Med 2009, 169(6):551-561Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials.

• 12 RCTs for nonvertebral fractures (two with ergocalciferol, ten with cholecalciferol, n=42.279 > 65 yr)

• 8 RCTs for hip fractures (n=40 886)

• The anti fracture efficacy of vitamin D increased significantly with higher received dose or higher achieved 25-hydroxyvitamin D levels (> 75nmol/l) for any nonvertebral fractures and for hip fractures

• No fracture reduction for a dose of 400 IU/d or less, 482 to 770 IU/d of supplemental vitamin D reduced nonvertebral fractures by 20% and hip fractures by 18%.

• better fracture reduction with cholecalciferol compared with ergocalciferol, whereas additional calcium did not further improve antifracture efficacy

Bischoff-Ferrari. Arch Intern Med 2009, 169(6):551-561Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials.

• 12 RCTs for nonvertebral fractures (two with ergocalciferol, ten with cholecalciferol, n=42.279 > 65 yr)

• 8 RCTs for hip fractures (n=40 886)

• The anti fracture efficacy of vitamin D increased significantly with higher received dose or higher achieved 25-hydroxyvitamin D levels (> 75nmol/l) for any nonvertebral fractures and for hip fractures

• No fracture reduction for a dose of 400 IU/d or less, 482 to 770 IU/d of supplemental vitamin D reduced nonvertebral fractures by 20% and hip fractures by 18%.

• better fracture reduction with cholecalciferol compared with ergocalciferol, whereas additional calcium did not further improve antifracture efficacy

• => higher dose or higher 25(OH)D levels (> 75nmol/l)

Bischoff-Ferrari. Arch Intern Med 2009, 169(6):551-561

Avenell - Cochrane Database Syst Rev 2009(2):CD000227Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

• Vitamin D alone appeared unlikely to be effective in preventing:

• hip fracture (9 trials, 24,749 participants, RR 1.15 (0.99 -1.33)

• vertebral fracture (5 trials, 9138 participants, RR 0.90 (0.42-1.92)

• any new fracture (10 trials, 25,016 participants, RR 1.01 (0.93-1.09)

• Vitamin D with calcium reduced hip fractures (eight trials, 46,658 participants, RR 0.84, 95% CI 0.73 to 0.96)

Avenell - Cochrane Database Syst Rev 2009(2):CD000227Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

• Vitamin D alone appeared unlikely to be effective in preventing:

• hip fracture (9 trials, 24,749 participants, RR 1.15 (0.99 -1.33)

• vertebral fracture (5 trials, 9138 participants, RR 0.90 (0.42-1.92)

• any new fracture (10 trials, 25,016 participants, RR 1.01 (0.93-1.09)

• Vitamin D with calcium reduced hip fractures (eight trials, 46,658 participants, RR 0.84, 95% CI 0.73 to 0.96)

• => vitamin D + calcium

DIPART group. BMJ 2010, 340:b5463Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe.

• 7 RCT of vitamin D with calcium or vitamin D alone

• 68.517 participants, mean 69.9 years

• vitamin D with calcium – overall RR 0.92, (0.86-0.99, p=0.025)

• hip fracture – RR 0.84 (0.70-1.01, P=0.07)

• vitamin D given alone in doses of 400-800 IU per day was not effective in preventing fractures

DIPART group. BMJ 2010, 340:b5463Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe.

• 7 RCT of vitamin D with calcium or vitamin D alone

• 68.517 participants, mean 69.9 years

• vitamin D with calcium – overall RR 0.92, (0.86-0.99, p=0.025)

• hip fracture – RR 0.84 (0.70-1.01, P=0.07)

• vitamin D given alone in doses of 400-800 IU per day was not effective in preventing fractures

• => vitamin D + calcium

Tang et al. Lancet 2007; 370: 657–66

Dietary intake – hip#

Bischoff , Am J Clin Nutr 2007;86:1780 –90

Intervention calcium vs placebo on NV# and hip#

Bischoff , Am J Clin Nutr 2007;86:1780 –90

Bolland et al. meta-analyse, BMJ 2010.39440.525752.BE

• 11 RCTs met bijna 12.000 deelnemers, leeftijd 72 jaar, 83% vrouw

• serum 25 OH-D 65 nmol/l

• calcium supplementen ≥ 500 mg per dag vs placebo gedurende 4 jaar zonder vitamine D.

• RR myocardinfarct: 1.27 (CI 1.01 tot 1.59, P=0.038)

• Het risico op herseninfarct, mortaliteit en het samengestelde eindpunt van myocardinfarct, CVA en mortaliteit was niet significant verhoogd

• 11 RCTs met bijna 12.000 deelnemers, leeftijd 72 jaar, 83% vrouw

• serum 25 OH-D 65 nmol/l

• calcium supplementen ≥ 500 mg per dag vs placebo gedurende 4 jaar zonder vitamine D.

• RR myocardinfarct: 1.27 (CI 1.01 tot 1.59, P=0.038)

• Het risico op herseninfarct, mortaliteit en het samengestelde eindpunt van myocardinfarct, CVA en mortaliteit was niet significant verhoogd

• Analyse van 5 van de 11 trials met daarin ruim 8.000 patiënten, met data op patiënt niveau: alleen een verhoogd risico gevonden bij dieetinname van 805 mg/dag; RR 1.85, (CI 1.28 - 2.67)

• Calcium supplement ≥ 1000 mg per dag behoudens 108 patiënten uit 1 trial die 600 mg/dag gebruikten

Bolland et al. meta-analyse, BMJ 2010.39440.525752.BE

Annual high-dose (500.000 IU vs placebo) oral vitamin D and falls and fractures in 2256 women >70 yrs

• Sanders K et al JAMA 2010; 303: 1815-22

Calcium en vitamine D-suppletie: discussiepunten

- Vitamine D: dosering of spiegel

- Dagelijks of bolus- Advies op basis van fractuurreductie bij interventie vs

placebo (en niet in combinatie met anti-osteoporose therapie)

- Calcium: - corrigeer vitamine D

- suppletie op basis van voedingsanamanese

- 500 mg is veelal voldoende