Calcium Supplementation in Postmenopausal Women to Reduce the Risk of Osteoporotic Fractures

Mikayla Spangler, Pharm.D., BCPS; Beth Bryles Phillips, Pharm.D., FCCP, BCPS; Mary B. Ross, M.B.A.; Kevin G. Moores, Pharm.D.

Disclosures

Am J Health Syst Pharm. 2011;68(4):309-318.

Benefits of Calcium and Vitamin D

Calcium is essential for various body functions, such as nerve impulse transmission, muscle contraction, and blood clotting. About 99% of calcium is found in the skeletal system but is leeched from the bones when the plasma calcium concentration is low. With low blood levels of calcium, parathyroid hormone is secreted, leading to the synthesis of calcitriol, which results in bone resorption and the release of calcium; if abundant calcium is present in the serum, this cycle will not occur and bone turnover will return to normal levels.^[23] Due to a decrease in estrogen production after menopause, women's bodies are less able to retain calcium from dietary sources.^[24] Calcium supplementation has been used for decades to prevent this calcium depletion, maintain bone mass, and prevent and treat osteoporosis. Because peak bone mass is achieved between the ages of 25 and 35 and slowly declines thereafter, calcium supplementation is recommended for women of all ages who are unable to meet dietary calcium recommendations.^[1] Because calcium intake tends to decrease with age, calcium supplementation is especially important in postmenopausal women. Vitamin D is also fundamental to bone health, because it is essential for optimal calcium absorption. Vitamin D production by the skin also declines with age, so older individuals require more vitamin D through dietary means or supplementation. Both calcium and vitamin D are important in regulating age-related increases in parathyroid hormone and bone resorption.^[25]

Calcium is best absorbed from food sources, but most postmenopausal women do not consume enough calcium and must use supplements to achieve the recommended amount. On average, U.S. adults consume 600 mg of elemental calcium per day, far below the recommended intake.^[26] There are a number of general guidelines on how much calcium postmenopausal women should consume. A consensus statement issued in 1994 by the National Institutes of Health (NIH) recommends 1500 mg of elemental calcium per day, obtained from dietary sources or supplements, for postmenopausal women; for those under age 65 years who are taking hormone replacement therapy, the recommended daily calcium intake is 1000 mg.^[27] These guidelines also recommend 600–800 IU of vitamin D per day. NIH has also stated that without sufficient calcium and vitamin D, other treatments for osteoporosis cannot improve bone architecture. Another guideline comes from the Institute of Medicine (IOM) Food and Nutrition Board, which recommends 1200 mg of elemental calcium per day.^[28] That panel also recommends 400 IU of vitamin D per day for patients 51–70 years of age and 600 IU daily after age 71. The National Osteoporosis Foundation^[29] (NOF) and AACE^[1] support the IOM recommendation on postmenopausal calcium intake. NOF recommends 800–1000 IU of vitamin D after age 50; AACE recommends 800 IU for the elderly.

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Cite this: Calcium Supplementation in Postmenopausal Women to Reduce the Risk of Osteoporotic Fractures - Medscape - Feb 15, 2011.

Table 1. Randomized Controlled Trials Evaluating Effects of Calcium Supplementation on Fracture Risk in Postmenopausal Women^a
Reference	Study Population	Treatment	BMD Changes per Intention-to-Treat Analysis	Effects on Incident Fractures or Fracture Risk
Reference	Study Population	Treatment	BMD Changes per Intention-to-Treat Analysis	Per Intention-to-Treat Analysis	Per Protocol Analysis
10	78 healthy women; mean age, 58 yr; median dietary calcium intake, 700 mg at baseline, 670 mg at 2 yr, 640 mg at 4 yr	Calcium lactate–gluconate + calcium carbonate (1,000 mg elemental calcium) daily or placebo for 4 yr	Increase in total body BMD over 4 yr greater with calcium vs. placebo (p = 0.002). Significant treatment effects also seen over 4 yr at lumbar spine (p = 0.03), femoral neck (p = 0.03), and trochanter (p = 0.01)	Incident fractures (all sites) Calcium: 2 Placebo: 7 (p < 0.05)	NA
11	197 women, 47% with preexisting fractures; mean age, 74 yr; mean baseline dietary calcium intake, 432 mg	Calcium carbonate (480 mg elemental calcium) per day or placebo for 4.3 ± 1.1 yr	Change in forearm BMD with preexisting fracture Calcium: 0.31% ± 0.25% per yr (p < 0.05) Placebo: −1.24% ± 0.38% per yr Change in forearm BMD with no preexisting fracture Calcium: 0 ± 0.26% per yr (p > 0.05) Placebo: −0.39% ± 0.27% per yr	Incident fractures with preexisting fracture Calcium: 15 Placebo: 21 (p < 0.05) Incident fractures with no preexisting fracture Calcium: 12 Placebo: 13 (p > 0.05)	NA
12	2,790 healthy women; mean age, 84 yr; baseline dietary calcium intake, 513 mg	Tricalcium phosphate (1,200 mg elemental calcium) + 800 IU vitamin D₃ per day or placebo for 1.5 yr	Change in femoral neck BMD at 1.5 yr Calcium: 2.7% Placebo: −4.6% (p < 0.001)	Nonvertebral fractures (no.) Treatment: 160 Placebo: 215 (p < 0.001) Hip fractures (no.) Treatment: 80 Placebo: 110 (p < 0.05)	Subgroup analysis (n = 1,765) of new fracture incidence, by fracture site Nonvertebral Treatment: 66 Placebo: 97 (p < 0.05) Hip Treatment: 21 Placebo: 37 (p < 0.05)
13	2,303 healthy women; mean age, 84 yr; baseline dietary calcium intake, 513 mg	Tricalcium phosphate (1,200 mg elemental calcium) + 800 IU vitamin D₃ per day or placebo for 3 yr	Not reported	Nonvertebral fractures (no.) Treatment: 255 Placebo: 308 (p < 0.05) OR for decreased probability of fracture, 0.72 (95% CI, 0.50–0.84) Hip fractures (no.) Treatment: 137 Placebo: 178 (p < 0.05) OR for decreased probability of fracture 0.73 (95% CI, 0.62–0.84)	Subgroup analysis (n = 1,765) of probability and OR (treatment vs. placebo) of new fracture, by fracture site/type Nonvertebral: −24% (p < 0.01); OR, 0.70 (95% CI, 0.51–0.91) Hip: −29% (p < 0.01); OR, 0.70 (95% CI, 0.62–0.78)
15	389 healthy women and men; mean age, 72 yr; baseline dietary calcium intake, 746 mg in women, 728 mg in men	Calcium citrate (500 mg elemental calcium) + 700 IU vitamin D per day or placebo for 3 yr	BMD change with treatment vs. placebo greater at femoral neck (0.5% vs. −0.7%; p = 0.02), lumbar spine (2.12% vs. 1.22%; p = 0.04), and for total body (0.06% vs. −1.09%; p < 0.001)	RR of first nonvertebral fracture with treatment vs. placebo, 0.4 (95% CI, 0.2–1.0; p < 0.05)	Cumulative incidence of first nonvertebral fracture Treatment: 5.9% Placebo: 12.9% (p < 0.05) RR (treatment vs. placebo) of first nonvertebral fracture, 0.5 (95% CI, 0.2–0.9)
16	583 women; mean age, 85 yr; baseline dietary calcium intake, 558 mg/day; baseline vitamin D intake, 41 IU/day	Tricalcium phosphate (1,200 mg elemental calcium) + 800 IU vitamin D₃ per day or placebo for 2 yr	Change in femoral neck BMD Calcium: 0.29% (p = 0.09) Placebo: −2.36%	Hip fracture incidence Treatment: 6.9% Placebo: 11.1% (p = 0.07) RR of hip fracture with treatment vs. placebo, 1.69 (95% CI, 0.96–3.00) Nonvertebral fracture incidence Treatment: 17.8% Placebo: 17.9% (difference NS)	NA
17, 30	36,282 healthy women; mean age, 62 yr; mean baseline calcium intake from all sources, 1,148–1,154 mg/day; mean baseline calcium intake from diet alone, 678 mg/day	Calcium carbonate (500 mg elemental calcium) + 200 IU vitamin D₃ twice daily or placebo for 9 yr	Increase in hip BMD at 9 yr 1.06% greater with treatment vs. placebo (p < 0.01); differences in spine and total body BMD changes with treatment vs. placebo at 9 yr NS	HR (treatment vs. placebo) for fracture, by fracture site Hip: 0.88 (95% CI, 0.72–1.08); NS Vertebra: 0.90 (95% CI, 0.74–1.10); NS Lower arm or wrist: 1.01 (95% CI, 0.90–1.14); NS All sites: 0.96 (95% CI, 0.91–1.02); NS	HR (treatment vs. placebo) for fracture, by fracture site Hip: 0.71 (95% CI, 0.52–0.97) Vertebra: 0.89 (95% CI, 0.67–1.19) Lower arm or wrist: 1.05 (95% CI, 0.90–1.23) Total fractures: 0.94 (95% CI, 0.87–1.02)
18	1,471 healthy women; mean age, 74 yr; baseline daily calcium intake, 861 mg in treatment group, 853 mg in placebo group	Calcium citrate (500 mg elemental calcium) twice daily or placebo for 5 yr	BMD increases at 5 yr with calcium vs. placebo 1.6% greater for hip (p < 0.0001), 1.8% greater for lumbar spine (p < 0.0001), and 1.2% greater for total body (p < 0.0001)	HR (treatment vs. placebo) for fracture, by fracture site/type Hip: 3.55 (95% CI, 1.31–9.63) Symptomatic: 0.91 (95% CI, 0.71–1.17); NS Osteoporotic: 0.87 (95% CI, 0.67–1.14); NS Vertebra: 0.72 (95% CI, 0.44–1.18); NS Distal forearm: 0.64 (95% CI, 0.40–1.03); NS	HR (treatment vs. control) for fracture, by fracture site/type Hip: 2.12 (95% CI, 0.72–6.19) Symptomatic: 0.87 (95% CI, 0.67–1.14); NS Osteoporotic: 0.83 (95% CI, 0.62–1.10); NS Vertebra: 0.61 (95% CI, 0.33–1.11); NS Distal forearm: 0.43 (95% CI, 0.22–0.85)
19	1,460 women; mean age, 75 yr; baseline daily calcium intake, 909 mg in treatment group, 934 mg in placebo group	Calcium carbonate (240 mg elemental calcium) twice daily or placebo for 5 yr	NA	HR (treatment vs. placebo) for fracture, by site Upper limb: 0.93 (95% CI, 0.56–1.54); NS Wrist or hand: 1.10 (95% CI, 0.60–2.02); NS Rib or pelvis: 0.99 (95% CI, 0.55–1.78); NS Proximal femur: 1.84 (95% CI, 0.68–4.96); NS Lower limb: 0.58 (95% CI, 0.32–1.03); NS Any appendicular site: 0.88 (95% CI, 0.65–1.18); NS Spine: 0.98 (95% CI, 0.63–1.54); NS Any site: 0.87 (95% CI, 0.67–1.12); NS	HR (treatment vs. placebo) for fracture, by fracture site Upper limb: 0.44 (95% CI, 0.21–0.92) Any appendicular site: 0.65 (95% CI, 0.43–0.97) Any site: 0.66 (95% CI, 0.45–0.97) Wrist or hand: 0.81 (95% CI, 0.35–1.88); NS Rib or pelvis: 0.71 (95% CI, 0.33–1.55); NS Proximal femur: 1.64 (95% CI, 0.39–6.87); NS Lower limb: 0.54 (95% CI, 0.25–1.18); NS Spine: 1.10 (95% CI, 0.42–2.84); NS
20	3,314 women with at least one risk factor for osteoporosis; mean age, 77 yr; baseline daily calcium intake, 1,075–1,084 mg	Calcium carbonate (500 mg elemental calcium) + 400 IU vitamin D twice daily for 2 yr + informational leaflet or leaflet only	NA	HR (treatment vs. control) for fracture, by fracture site Hip: 0.75 (95% CI, 0.31–1.78); NS Hip and wrist: 0.89 (95% CI, 0.56–1.44); NS All fractures: 1.01 (95% CI, 0.71–1.43); NS	HR (treatment vs. control) for all fracture sites, 1.03 (95% CI, 0.68–1.56); NS
21	5,292 men and women (85% women) with previous osteoporotic fracture; mean age, 77 yr; baseline daily calcium intake not reported	Calcium carbonate (1,000 mg elemental calcium) alone vs. calcium carbonate + 800 IU vitamin D₃ or placebo for 2–5 yr	NA	HR for new low-trauma fracture, by treatment variable Calcium carbonate vs. no calcium carbonate: 0.94 (95% CI, 0.81–1.09); NS Vitamin D₃ vs. no vitamin D₃: 1.01 (95% CI, 0.88–1.17); NS Calcium carbonate + vitamin D₃ vs. placebo: 1.01 (95% CI, 0.75–1.36); NS	HR for new fracture, by treatment variable Calcium carbonate vs. no calcium carbonate: 1.01 (95% CI, 0.70–1.48) Vitamin D₃ vs. no vitamin D₃: 1.01 (95% CI, 0.70–1.45)

^aBMD = bone mineral density, CI = confidence interval, HR = hazard ratio, NA = not applicable, NS = not significant, OR = odds ratio, RR = relative risk.

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