An update on osteoporosis research: effect of calcium plus vitamin D supplementation

Lincon Chandra Shill, Nafisa Habib Purba, Marjia Sultana, Towhid Hasan, Mahmudur Rahman, Nahid Sultana


Osteoporosis is the most common systemic skeletal disease characterized by increased bone fragility. There lies an incongruity among research regarding combined supplementation of calcium (Ca) plus vitamin D and loss of bone health. Hence, the present review is aimed to highlight the current development of osteoporosis research and try to solve the inconsistency among the present knowledge. Electronic databases like PubMed, Cochrane Library, and EMBASE were searched from their inception to December 2018 using terms “calcium,” “vitamin D,” and “osteoporosis.” A systemic approach was followed to reach a final of 23 studies assessing the synergetic effect of calcium and vitamin D on osteoporosis and fractures risk. Among the included studies, nineteen have revealed that calcium and vitamin D decrease bone resorption, reduce the incidence of fractures, increase bone mineral density (BMD) and overall bone health. However, no significant osteogenic response was reported in five trials after supplementation with calcium and vitamin D together. Osteoporosis results in a reduced quality of life, increased disability-adjusted life span, and big economic burden to health care systems of countries. Early diagnosis before the occurrence of fractures and by assessing BMD and with early treatment, osteoporosis can be prevented. It is not entirely possible to draw a conclusion regarding beneficial effects of calcium plus vitamin D supplementation; future research based on the fundamentals of bone biology focusing on molecular genetics, and influencing factors of the acquisition of bone mass during growth and bone loss can alleviate present controversies.


Osteoporosis, Calcium, Vitamin D

Full Text:



Chen LR, Wen YT, Kuo CL, Chen KH. Calcium and vitamin D supplementation on bone health: current evidence and recommendations. Int J Gerontol. 2014;8(4):183-8.

WHO. Prevention and management of osteoporosis. World Health Organization: Geneva, Switzerland; 2003.

WHO. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. World Health Organization: Geneva, Switzerland; 1994.

Sozen T, Ozisik L, Basaran NC. An overview and management of osteoporosis. Eur J Rheumatol. 2017;4(1):46-56.

Reginster JY, Burlet N. Osteoporosis: a still increasing prevalence. Bone. 2006;38(2):4-9.

Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014;29(11):2520-6.

Watts NB, Bilezikian JP, Camacho PM, Greenspan SL, Harris ST, Hodgson SF, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis: executive summary of recommendations. Endocr Pract. 2010;16(6):1016-9.

Lau EM, Lee JK, Suriwongpaisal P, Saw SM, Das De S, Khir A, et al. The incidence of hip fracture in four Asian countries: the Asian Osteoporosis Study (AOS). Osteoporos Int. 2001;12(3):239-43.

Weaver CM. Calcium supplementation: is protecting against osteoporosis counter to protecting against cardiovascular disease? Curr Osteoporos Rep. 2014;12(2):211-8.

Laird E, Ward M, McSorley E, Strain JJ, Wallace J. Vitamin D and bone health: potential mechanisms. Nutrients. 2010;2(7):693-724.

Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22(3):465-75.

Bailey RL, Dodd KW, Goldman JA, Gahche JJ, Dwyer JT, Moshfegh AJ, et al. Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr. 2010;140(4):817-22.

Wallace TC, Reider C, Fulgoni VL. Calcium and vitamin D disparities are related to gender, age, race, household income level, and weight classification but not vegetarian status in the United States: Analysis of the NHANES 2001-2008 data set. J Am Coll Nutr. 2013;32(5):321-30.

Jowsey J, Riggs BL, Kelly PJ, Hoffmann DL. Effect of combined therapy with sodium fluoride, vitamin D and calcium in osteoporosis. Am J Med. 1972;53(1):43-9.

Riggs BL, Jowsey J, Kelly PJ, Hoffman DL, Arnaud CD. Effects of oral therapy with calcium and vitamin D in primary osteoporosis. J Clin Endocrinol Metab. 1976;42(6):1139-44.

Inkovaara J, Gothoni G, Halttula R, Heikinheimo R, Tokola O. Calcium, vitamin D and anabolic steroid in treatment of aged bones: double-blind placebo-controlled long-term clinical trial. Age Ageing. 1983;12(2):124-30.

Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med. 1992;327(23):1637-42.

Eriksson SA, Lindgren JU. Combined treatment with calcitonin and 1,25-dihydroxyvitamin D3 for osteoporosis in women. Calcif Tissue Int. 1993;53(1):26-8.

Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997;337(10):670-6.

Baeksgaard L, Andersen KP, Hyldstrup L. Calcium and vitamin D supplementation increases spinal BMD in healthy, postmenopausal women. Osteoporos Int. 1998;8(3):255-60.

Krieg MA, Jacquet AF, Bremgartner M, Cuttelod S, Thiebaud D, Burckhardt P. Effect of supplementation with vitamin D3 and calcium on quantitative ultrasound of bone in elderly institutionalized women: a longitudinal study. Osteoporos Int. 1999;9(6):483-8.

Ringe JD, Coster A, Meng T, Schacht E, Umbach R. Treatment of glucocorticoid-induced osteoporosis with alfacalcidol/calcium versus vitamin D/calcium. Calcif Tissue Int. 1999;65(4):337-40.

Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res. 2000;15(6):1113-8.

Son SM, Chun YN. Effect of oral therapy with alphacalcidol or calcium in Korean elderly women with osteopenia and low dietary calcium. Nutr Res. 2001;21(10):1347-55.

Chapuy MC, Pamphile R, Paris E, Kempf C, Schlichting M, Arnaud S, et al. Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Osteoporos Int. 2002;13(3):257-64.

Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003;18(2):343-51.

Doetsch AM, Faber J, Lynnerup N, Watjen I, Bliddal H, Danneskiold-Samsoe B. The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: a randomized placebo-controlled study. Calcif Tissue Int. 2004;75(3):183-8.

Harwood RH, Sahota O, Gaynor K, Masud T, Hosking DJ. A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. Age Ageing. 2004;33(1):45-51.

Larsen ER, Mosekilde L, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. J Bone Miner Res. 2004;19(3):370-8.

Meier C, Woitge HW, Witte K, Lemmer B, Seibel MJ. Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. J Bone Miner Res. 2004;19(8):1221-30.

Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, et al. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet. 2005;365(9471):1621-8.

Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, et al. Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ. 2005;330(7498):1003.

Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669-83.

Bolton-Smith C, McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, et al. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res. 2007;22(4):509-19.

Kukuljan S, Nowson CA, Bass SL, Sanders K, Nicholson GC, Seibel MJ, et al. Effects of a multi-component exercise program and calcium-vitamin-D3-fortified milk on bone mineral density in older men: a randomised controlled trial. Osteoporos Int. 2009;20(7):1241-51.

Salovaara K, Tuppurainen M, Karkkainen M, Rikkonen T, Sandini L, Sirola J, et al. Effect of vitamin D(3) and calcium on fracture risk in 65- to 71-year-old women: a population-based 3-year randomized, controlled trial--the OSTPRE-FPS. J Bone Miner Res. 2010;25(7):1487-95.