The role of calcium and vitamin D in bone health in the general population. Bess Dawson-Hughes, M.D.
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1 The role of calcium and vitamin D in bone health in the general population Bess Dawson-Hughes, M.D.
2 Risk Factors for Osteoporosis MODIFIABLE Sedentary Poor diet Ca, vit D Smoking Excess alcohol Early loss of estrogen Thinness NOT MODIFIABLE Age Heredity Medications- e.g., steroids Prior hip or spine fx
3 Basis for Setting Calcium Intake RDA (amount required for maximal calcium retention from balance studies) % Maximal retention Spencer H, 1984 Jackman L, 1997 Calcium intake (mg/day)
4 Calcium Intake and Risk of Hip Fracture (in 61,433 Swedish Women in Mammography Cohort) Warensjo E. Br Med J 2011;342:d1473.
5 Calcium Supplementation and Hip Fracture Risk (170,991 men and women, 2954 fractures) Women RR 1.01 [0.97, 1.05] Men RR 0.92 [0.82, 1.03] Bischoff-Ferrari H. AJCN 2010;86:
6 Calcium Supplementation and Non-vertebral Fracture Risk in Men and Women RR = 0.92 [0.81, 1.05] Bischoff-Ferrari H. AJCN 2010;86:
7 Food vs supplemental calcium and stone risk Results of Observational Study Q1 Q5 Food Ca <488 mg >1098 mg * Supp Ca 0 mg >500 mg * * P for trend < 0.05 Curran GC. Ann Int Med 1997;126:497
8 Safety of Ca Supplements Kidney Stones in WHI Ca + D Placebo Wallace RB. AJCN 2011;doi /ajcn
9 Effect of Calcium Supplements on Risk of MI (RCT:45 events in 31 women vs 19 events in 14 women, P=0.01) Bolland MJ. BMJ 2010;341:c3691; doi: /bmj.c3691.
10 Effect of Calcium Supplements on Risk of MI Bolland MJ. BMJ 2010;341:c391;doi: /bmj.c3691.
11 Ca supplement use is associated with increased risk of MI Heidelberg cohort: 23,980 adults aged yrs followed for 11 years HR for Ca supplement use: 1.86 [1.17, 2.96] Li K. Heart 2012; 98:
12 Association of calcium intake with coronary artery calcification Framingham Off-spring; mean age 60 yrs; 690 women (open bars) and 588 men (filled) Samuelson EJ. Am J Clin Nutr 2012;96:
13 WHI ANALYSIS In the WHI study (n = 36282, randomized to receive 1000 mg Ca/400 IU D daily or placebo [mean baseline Ca intake ~1150 mg/d]), there was no effect of Ca/D on coronary or cerebrovascular events MI/CAD death HR = 1.04 ( ); Stroke HR = 0.95 ( ) In subgroup analyses, no interaction with higher total Ca intake at baseline Hsia et al. Circulation 115:846, 2007
14 Ca Supplementation and Risk of Atherosclerotic Vascular Disease 5-yr RCT + 4 yr F/U in 1460 women, mean age 75 yr; 1200 mg/d Ca vs P Lewis JR. JBMR 2011;26: HR = 0.919, [0.737, 1.146]
15 Calcium RDA IOM 2011 Men Women Age mg/d Age mg/d Age mg/d Age mg/d
16 Dietary Reference Intakes. IOM 2011.
17 Calcium recommendations Goal: RDA ( mg/d) Food sources first choice Use supplements to bring TOTAL intake to 1000 to 1200 mg Rarely is more than 500 to 600 mg of supplemental calcium needed
18 Vitamin D Insufficiency Ca absorption Muscle mass PTH Muscle strength Bone TO and loss Falls Fractures
19 NHANES III Serum 25(OH)D and Performance Walk time Sit-to-stand Bischoff-Ferrari HA. Am J Clin Nutr 2004;80:752-8.
20 Effect of Vitamin D 3 on Falls (124 nursing home residents, mean age 89 years, 5 mo follow-up) 60 Proportion of fallers Vitamin D dose, IU/d Broe KE. JAGS 2007;55:234-9.
21 2.5 Broe 200 IU Broe 600 IU 2.0 Broe 400 IU RR (95% CI) Broe 800 IU Bischoff IU Pfeifer IU Bischoff Ferrari 700 IU 0.5 Pfeifer IU Achieved 25(OH)D serum concentration in treatment group (nmol/l) Bischoff-Ferrrari. Br Med J 2011.
22 Vitamin D and Falls (RCT in 173 acute hip fracture patients 800 vs 2000 IU/d for 1 yr) Doses and 25OHD levels: 800 IU group (39 88 nmol/l) 2000 IU group ( nmol/l) Outcome: No difference in first fallers or number of falls in the two dose groups Bischoff-Ferrari H. Archiv of Int Med 2010;170:
23 Effect of High Dose Vitamin D on Falls and Fractures in 2,256 Women age 70+ (500,000 IU orally once per year) Sanders KM. JAMA 2010;303:
24 Summary - Falls 25OHD levels of nmol/l (26 36 ng/ml) are associated with a 15-20% decrease in risk of falling. Increasing 25OHD levels above this range doesn t appear to add benefit. High annual doses of vitamin D increase risk of falling.
25 Serum PTH and 25(OH)D Vary Inversely (STOP/IT 387 healthy men and women age 65 years and older) Durazo-Arvizu RA. J Nutr, 2010;140:595-9.
26 Vitamin D Supplementation and Bone Mineral Density Meta-analysis of 23 RCTs Reid I. Lancet 2013; doi.org/ /s (13)
27 Impact of Vitamin D and Calcium on Femoral Neck BMD in Men age 65+ Dawson-Hughes B et al. Am J Clin Nutr 2000; 72:
28 Vitamin D and fracture prevention Individual Subject Level Meta-analysis of RCTs 31,022 persons, 91% women, 11 RCTs Mean age 76 years (all age 65+) 1111 hip fxs, 3770 non-vertebral fxs Actual D intake (personal supplements, study pills x compliance) Bischoff-Ferrari H. NEJM 2012;367:40-49.
29 Intent-to-Treat Analysis Hip fracture RR 0.90 [ ] Non-vert fracture RR 0.93 [ ] Bischoff-Ferrari H. NEJM 2012;367:40-49.
30 Risk of Fracture by quartile of vitamin D intake Meta-analysis of individuals from RCTs (31,022 persons, mean age 76 yrs) Bischoff-Ferrari H. NEJM 2012;367:40-49.
31 Effect of vitamin D as a function of age, dwelling and calcium supplement use Bischoff-Ferrari H. NEJM 2012;367:40-49.
32 Spinal bone loss over 1-2 yr in women with breast cancer taking calcium and vitamin D Premenopausal women Postmenopausal women Datta M. Crit Rev Oncol Hematol 2013; doi.org/ /j.critrevonc
33 Role of calcium and vitamin D in patients on pharmacotherapy for osteoporosis
34 Fracture Prevention Trials: Calcium and Vitamin D Use and Results Drug/Study Ca, mg/d Vit D, IU/d Fracture risk reduction (RR) Alendronate Liberman Black * Cummings * Risedronate Harris 99 1, Raloxifene Ettinger * If dietary calcium < 1,000 mg If 25(OH)D level < 40 nmol/l
35 IOM Vitamin D Age / EAR/RDA D intake IU/d Target 25OHD, nmol/l Functional indicator Bone health EAR RDA Fractures EAR RDA
36 IOF Position Statement Vitamin D Recommendations for Older Adults Adults with little regular sun exposure should take 800 to 1000 IU/d of vitamin D3. At risk groups for deficiency should have 25OHD measured and be supplemented in amounts needed to reach serum 25OHD level of 75 nmol/l. IOF Position Statement. Dawson-Hughes B et al. Osteoporosis Int 2010;21:
37 Individuals at Increased Risk for Low 25OHD Levels Osteoporosis Obese Little sun exposure Dark skin High latitude Sunscreen use Malabsorption Anti-epileptics (increase metabolism)
38 To Increase serum 25OHD with vitamin D: 1 mcg 0.7 to 1.1 nmol/l 100 IU 0.7 to 1.1 ng/ml
39 Serum 25(OH)D Responses to 1000 (A) and 4000 (B) IU/d of Vitamin D 3 A B Vieth R. Am J Clin Nutr 2001; 73:
40 Effects of the same cumulative dose of vitamin D 3, equivalent to 1500 IU/d, but given once daily, once weekly, or once monthly, on serum 25(OH)D Ish-Shalom, S. et al. J Clin Endocrinol Metab 2008;93:
41 Impact of vitamin D2 and D3 on serum 25OHD 1600 IU daily (left) and 50,000 IU monthly (right) Binkley N. JCEM 2011;96:
42 Conclusions - Calcium A total calcium intake of 1000 to 1200 is sufficient for bone health and more isn t better. Exceeding this amount through supplement use may increase risk of kidney stones and possibly CV disease. There is no suggestion that calcium from food sources is risky. Therefore meeting the calcium requirement through diet is recommended.
43 Conclusions Vitamin D A mean intake of 800 IU per day (resulting in a 25OHD level of nmol/l) lowers risk of falling by about 20% in older adults. Higher doses do not provide additional benefit. A mean intake of 800 IU per day (resulting a 25OHD level > 60 nmol/l) lowers hip fracture risk by up to 30% and non-vertebral fracture risk by 14% in both general and high risk older populations. High annual oral doses increase risk of falls and fractures. High risk patients should have 25OHD measured and doses titrated as needed to reach target; others should be supplemented with 800 to 1000 IU of D3 per day.
44 Conclusions (3) Calcium and vitamin D alone have not been tested in cancer patients, but observational studies reveal that they are not sufficient to prevent bone loss in breast cancer patients and others with gonadal insufficiency. However, they are essential components of any regimen to prevent bone loss in these patients.
45 Bolland reanalysis of WHI Hypothesis: Ca supplement use may obscure adverse effect of Ca on CVD Baseline MI rate, % No personal Ca use Any personal Ca use CaD P CaD P HR 1.20 [0.99,1.47] 0.94 [0.77,1.114] Bolland MJ. BMJ 2011;342:d2040 doi: /bmj.d2040.
46 Effect of Exercise on Bone Density Bassey EJ, et al. J Bone Miner Res 1998; 13: Heinonen A, et al. Lancet 1996; 348: Lohman T, et al. J Bone Miner Res 1995; 10: Snow-Harter C, et al. Bone Miner Res 1992; 7:
47 Effect of Tai Chi on Risk of Falling Home-based program, 15 min/d for 15 wks in 200 men and women age 70+ Wolff SL. J Am Geriatr Soc 1996;44:
48 Calcium and Vitamin D Intakes and Serum PTH Icelandic population, males (58 ± 14 yrs) and females (54 ± 16 yrs) Serum Parathyroid hormone (pg/ml) Calcium intake (mg/d) < >1200 < > 45 Serum 25- Hydroxyvitamin D (nmol/l) Steingrimsdottir L, JAMA 2005; 294:
49 Relative importance of 25(OH)D status and calcium intake with respect to hip BMD (n=4958) P-value for trend across categories of 25(OH)D levels: < Adjustments: calcium intake, age, race/ethnicity, body mass index, height, total calorie intake, estrogen use among women, physical activity, smoking, and socio-economic status. Bischoff-Ferrari HA, et al.; JBMR 2009; 24:
50 Vitamin D Content of Foods Food mcg IU Salmon (3.5 oz) Tuna (3.5) Egg (1) Liver (3.5 oz) Ref: USDA database.
51 Forbes, 1979
52 Effect of Estrogen Calcium on BMD (Meta-analysis of 31 estrogen trials) Estrogen Alone Estrogen + Calcium Number of trials Years since menopause Calcium intake, mg , Nieves JW. Am J Clin Nutr 1998; 67:
53 Effect of Estrogen Calcium on Change in BMD Nieves JW. Am J Clin Nutr 1998; 67:
54 Calcitonin, Calcium and Vertebral Fracture Risk MEDOS Study 1 * Calcitonin Calcium Ca + Calcitonin *P=0.01 Kanis JA. Br Med J 1992; 305;
55 Vitamin D - Clinical Considerations - Who is at risk for low 25OHD? - Who should be measured? - Supplementing to target level - Dosing frequency - D2 vs D3
56 Calcium Supplementation for the Prevention of Postmenopausal Bone Loss:a meta-analysis (Weighted mean difference for lumbar spine after treatment with calcium at 2 yr) Shea B, et al. Endocrine Rev. 2002,23(4):
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