V t i amin i n D a nd n d Calc l iu i m u : Rol o e l in i n Pr P eve v nt n io i n and n d Tr T eatment n of o Fr F actur u es and n d Fa F ll l s

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1 Vitamin D and Calcium: Role in Prevention and Treatment of Fractures and Falls Osteoporosis 21: New Insights In Research, Diagnosis, and Clinical Care Deborah Sellmeyer, MD Director, Johns Hopkins Metabolic Bone Center Dept of Medicine, Division of Endocrinology Meta-analysis analysis of calcium +/- vitamin D 29 studies, 63,897 participants 92% women age years 17 reported fracture, 24 reported BMD 13 trials calcium + vitamin D Bone loss.54% (.35.73) hip 1.19% ( ) spine Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Lancet. 27 Aug 25;37(9588): Meta-analysis analysis of calcium +/- vitamin D No differences in fracture reduction Chapuy-1.75 ( ).87) Reid.4 ( ) Chevalley.96 ( ) Recker.85 ( ) Dawson-Hughes.46 (.23-.9).9) Riggs.89 ( ) 1.57) Peacock.81 ( ) Chapuy-2.85 ( ) Larsen.84 ( ).98) Harwood.49 ( ) Fujita.31 ( ) RECORD-1.94 ( ) Porthouse.96 ( ) RECORD-2.94 ( ) Jackson.97 ( ) Reid-2.92 ( ) Prince-1.87 ( ) Overall.88 ( ) 12% reduction in fracture risk, p=.4 Type of fracture Calcium alone vs. calcium + vitamin D Gender Favours treatment Favours control Page 1

2 Factors associated with higher effect Baseline low 25-OH vitamin D (< 1 ng/ml) Baseline calcium intake < 7 mg/day Institutionalized vs. community dwellers Age > 7 years Higher adherence Calcium doses > 12 mg Vitamin D doses > 8 IU Calcium and Vitamin D vs. Vitamin D 7 vitamin D trials US, Europe, >1 68,5 study participants Age 69.9, 14.7% men All trials.95 (.9 to 1.1) CaD trials.92 (.86 to.99 D trials 1.1 (.92 to 1.12) BMJ. 21 Jan 12;34:b5463. doi: /bmj.b5463 Effect on falls by dose and 25 OH D level Annual high dose vitamin D Falls Fractures RR (95% CI) Dose of vitamin D2 or D3 (IU) RR (95% CI) OH D serum concentrations (nmol/l) Falls, % HR 1.16 ( ), 1.28), p=.3 25 HR 1.26 ( ), p= No. of women Vitamin D Placebo Fractures, % Bischoff-Ferrari, et. al. BMJ. 29 Oct 1;339:b3692. doi: /bmj.b3692 Sanders, et. al. JAMA. 21 May 12;33(18): Page 2

3 Serum 25 OH vitamin D levels Median Serum 25-OH D (nmol nmol/l) Months Since Predose, 26 No. of women Vitamin D Placebo ng/ml 3 ng/ml Calcium Current recommendations up to age 5: 1 mg/day ages 51+: mg/day maximum: 25 mg/day Threshold nutrient 17% kidney stones in WHI Labels based on 1 mg 3% = 3 mg 25% = 25 mg Sanders, et. al. JAMA. 21 May 12;33(18): Calcium Active and passive absorption throughout small intestine Max intake at once ~ 5 mg Diet w/no calcium rich foods = 25 mg calcium Interferes with iron, thyroid hormone absorption Caffeine Soda ] OK in moderation with adequate calcium intake Dairy foods Sources of Calcium Lactose intolerance: hard cheeses, lactase treated dairy products Fortified cereal, OJ, cereal bars, soy/rice milk Tofu Dark green leafy vegetables broccoli, broccoli, cabbage, brussel sprouts, mustard greens Calcium Quiz Hacker et. al. J Am Diet Assoc 29;19: Page 3

4 Calcium Supplements Citrate vs. Carbonate Coral calcium = calcium carbonate USP verified Chewable Viactiv, GNC, Tums Vitamin D sufficient calcium absorp = 3% insufficient calcium absorp = 1% Vitamin D Prevalence of vitamin D deficiency 5% elderly hip fx patients 67% of inpatients > age 65 42% premenopausal African American women 4%-5% premenopausal Caucasian women 57% interns/residents in Brazil Current recommendations: up to age 5: 2 IU/day ages 51-7: 4 IU/day ages 71+: 6 IU/day maximum: 2 IU/day Regulated by PTH (parathyroid hormone) eggs prescription Ergocalciferol Page 4

5 Short term: D2 vs. D3 Longterm: D2 vs. D3 Change in 25(OH) D (nmol nmol/l) D 3 D Time (days) Armas et. al. J Clin Endocrinol Metab 89; Serum 25(OH) D (ng ng/ml) D 3 D 3 + D 2 D 2 Placebo Time (weeks) Holick et. al. J Clin Endocrinol Metab 93: , 28 Vitamin D Therapy Sources of vitamin D All osteoporosis therapeutic trials conducted with calcium/vitamin D Mixed results in literature Lower doses More replete populations Poor adherence Effects of intermittent dosing Target serum level = > 32 ng/ml Probably need > 8 IU/day 1, IU/day no adverse effects, 25-OH D levels ~ 9 ng/ml Hathcock, et al. Am J Clin Nutr 27;85:6-18 Sunshine: 2 minutes/day, 6% body surface Food Milk 1 IU/glass Cod liver oil: 453 IU/teaspoon Tuna in fish oil: 17 IU/ 1/2 cup Egg: 26 IU/large egg Supplements Multivitamin: 2-4 IU + GNC D3: 1,, 2, liquid (1 IU/drop), gummy (1, IU) D3: 1,, 5, (26 IU), 5, (3,) IU Page 5

6 Summary Calcium: 12 mg/day diet diet + supplements Vitamin D: 12 IU/day Be alert for conditions that might need more malabsorption (gastric bypass) healing osteomalacia fracture healing anabolic therapy adolescence post operative hyperparathyroid hypoparathyroid Page 6

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