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IOF position statement: vitamin D recommendations
for older adults - Position Paper
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Osteoporosis International
With other metabolic bone diseases
International Osteoporosis Foundation and National Osteoporosis Foundation July 2010
High Dose Vitamin D Increased Fall & Fracture Rate
12 May 2010 ... Although our results cannot necessarily be applied to high-dose vitamin D administered in divided dosesover the year, they suggest that ...
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Diagnosis and management of vitamin D deficiency
11 Jan 2010 ... Vitamin D status is most reliably determined by assay of serum ..... * Multivitamin preparations; not suitable for prolonged high dose ...
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B. Dawson-Hughes1 Contact Information, A. Mithal2, J.-P. Bonjour3, S. Boonen4, P. Burckhardt5, G. E.-H. Fuleihan6, R. G. Josse7, P. Lips8, J. Morales-Torres9 and N. Yoshimura10
(1) Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA
(2) Indraprastha Apollo Hospitals, Sarita Vihar, Delhi-Mathura Road, 110044 New Delhi, India
(3) University Hospital, Division of Bone Diseases, University Hospitals and Faculty of Medicine, Rue Micheli-du-Crest 24, 1211 Geneva, Switzerland
(4) Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Herestraat 49, 3000 Leuven, Belgium
(5) Association Suisse contre lÕOstŽoporose, Clinique Bois-Cerf, Avenue dÕOuchy 31, 1006 Lausanne, Switzerland
(6) Calcium Metabolism and Osteoporosis Program, American University of Beirut-Medical Center, Riad El Solh, PO BOX: 11-0236, 1107 2020 Beirut, Lebanon
(7) Division of Endocrinology and Metabolism, University of Toronto, St MichaelÕs Hospital Health Centre, 61 Queen Street East, Toronto, ON, M5C 2T2, Canada
(8) Division of Internal Medicine, Endocrine Section, VU University Medical Center, PO Box 7057, 1007, MB Amsterdam, Netherlands
(9) Hospital Aranda de la Parra, Hidalgo 329-704, Le—n, 37000, GTO, Mexico
(10) Department of Joint Disease Research, 22nd Century Medical and Research Center, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
Contact Information B. Dawson-Hughes
Email: bess.dawson-hughes@tufts.edu
Received: 9 March 2010 Accepted: 16 April 2010 Published online: 27 April 2010
Abstract
This position paper of the International Osteoporosis Foundation makes recommendations for vitamin D nutrition in elderly men and women from an evidence-based perspective.
This material is based in part upon work supported by the US Department of Agriculture, Agricultural Research Service, under agreement no. 58-1950-7-707. Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the US Department of Agriculture, the Centers for Disease Control and Prevention or the US Department of Health and Human Services.
This statement has been endorsed by the IOF Committee of Scientific Advisors
Introduction
Vitamin D is important for bone and muscle development, function, and preservation. The serum 25OHD concentration is the best available clinical indicator of vitamin D status. Until recently, optimal serum 25OHD concentration was considered to be that level associated with maximal parathyroid hormone (PTH) suppression. Estimates of that threshold level have clustered around 32-50 nmol/L (12.8-20 ng/ml) and 68-75 nmol/L (27.2-30 ng/ml), depending upon analytical approach used [1]. In the last decade, however, the evidence base for older men and women has grown to include many randomized, controlled clinical trials (RCTs) with falls and fracture endpoints. Because the RCTs have for the most part been conducted in men and women over the age of 60 to 65 years, our recommendations are directed at this large and growing older segment of the adult population. Our objective is to use available evidence to support recommendations for optimal vitamin D status. We approach this by examining the efficacy of different vitamin D doses administered and levels of 25OHD achieved in reducing risk of falls and fractures. In this process, it is important to consider other factors that influence serum 25OHD levels and responses to oral vitamin D supplementation.
Determinants of serum 25OHD levels and of the serum 25OHD response to oral vitamin D
Vitamin D intake and effective sun exposure are the major determinants of the serum 25OHD level. Several factors influence the increment in serum 25OHD in response to a given dose of vitamin D3, including the starting level of 25OHD. At a dose of 2.5 µg (100 IU/d), the mean increment ranges from 2.75 nmol/l (1.1 ng/ml) at low starting 25OHD levels to 1.75 nmol/l (0.7 ng/ml) at higher (near optimal) starting levels [2]. The increment in 25OHD in response to a given dose of vitamin D also varies with body size. It is smaller in subjects with high BMI than in individuals with normal BMI [3, 4]. Other factors affect 25OHD levels but have no known impact on 25OHD responses to supplemental vitamin D. Estrogen use increases measured serum 25OHD levels by increasing levels of vitamin D binding protein [5] but does not alter the serum 25OHD increment achieved with supplementation. Serum 25OHD levels decline with aging, but the serum 25OHD response to a given dose of supplemental vitamin D3 is not affected by age [6]. Similarly, the dietary calcium intake, within the range usually consumed, does not affect the serum 25OHD response to vitamin D supplementation [7]. (The latter statement should not be confused with the observations that the calcium requirement may be dependent upon vitamin D status and that an adequate calcium intake is important for bone health [8].) Finally, serum 25OHD levels vary widely across commonly used assays. Until this problem is addressed by widespread use of standard reference material such as the NIST standards [9] and participation in the DEQAS quality control program (www.deqas.org), assay variability will continue to complicate the process of determining the desired 25OHD level and the impact of a given dose on serum 25OHD levels.
Falls
Vitamin D is thought to act on myocyte vitamin D receptors to exert its effect on muscle tissue. In prospective studies, lower serum 25OHD levels have been associated with decreased grip strength and appendicular muscle mass in older men and women [10, 11] Supplementation with vitamin D has improved lower extremity muscle performance and reduced risk of falling in several high-quality double blind RCTs [12]. These trials have employed doses up to 25 µg (1,000 IU) of vitamin D per day, with and without calcium. Supplementation in amounts of 17.5 to 25 µg/day (700-1,000 IU/day) lowered risk of falling by 20% in older individuals, independent of their calcium intake level. In contrast, supplementation with doses of <17.5 µg/day (<700 IU/day) had no detectable effect on falls. From this meta-analysis of available data, it appears that a mean serum 25OHD level of at least 60 nmol/L (24 ng/ml) is needed for optimal fall risk reduction. Observational studies suggest that there may be benefit to increasing serum 25OHD levels beyond 60 nmol/L (24 ng/ml), but higher levels (and doses) have not been evaluated in RCTs.
Fractures
Vitamin D affects fracture risk through its effects on bone metabolism and on risk of falling. Randomized controlled trials indicate that supplementation with vitamin D reduces rates of bone loss in older women [13]. The impact of supplemental vitamin D on fracture risk has been examined mainly in men and women age 65 and older. A recent meta-analysis revealed that vitamin D in doses in the range of more than 10 through 20 µg/day (>400-800 IU/day) reduced risk of non-vertebral and hip fracture by approximately 20% whereas doses up through 10 µg/day (400 IU/day) had no evident effect [14]. Doses above 20 µg/day (800 IU/day) have not been studied. The mean serum 25OHD level associated with reduction in non-vertebral fracture risk was 66 nmol/L (26.4 ng/ml). Hip fracture risk reduction was observed at a mean 25OHD level of 74 nmol/L (29.6 ng/ml) and higher. Based on this and other evidence, eight of ten IOF Working Group members felt that 75 nmol/L (30 ng/ml) is the appropriate target level of serum 25OHD for older individuals; in contrast, two members felt that the target should be 50 to 75 nmol/l (20 to 30 ng/ml). The estimate of 75 nmol/l (30 ng/ml) is close to the higher cluster of 25OHD levels associated with maximal PTH suppression [1].
Other potential benefits
Vitamin D insufficiency has been implicated as a contributing factor in a growing number of important chronic diseases including type 2 diabetes, cardiovascular disease, selected cancers, and autoimmune diseases as well as infections, and also to increased mortality. RCTs are needed before causal relationships can be determined and optimal 25OHD levels for prevention can be established. The doses and mean serum levels needed to achieve optimal impact on these non-classical outcomes are not clear.
Global vitamin D status
Vitamin D insufficiency, whether defined as 25OHD levels <75 or <50 nmol/L (<30 or <20 ng/ml), is prevalent worldwide [15]. For instance, the prevalence of levels <75 nmol/L (<30 ng/ml) in postmenopausal women has been reported to be approximately 50% in Thailand and Malaysia, 75% in the USA, and 90% in Japan and South Korea. Vitamin D deficiency, defined as a level below 25 nmol/L (10 ng/ml) is very common in the Middle East and South Asia where mean levels range from 10 to 30 nmol/L (4 to 12 ng/ml) [15, 16]. The high prevalence of suboptimal 25OHD levels in older men and women around the world raises the possibility that many falls and fractures can be prevented with vitamin D supplementation.
Vitamin D preparations
Vitamin D is available in two forms, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Some find that the two forms are equally effective in raising the serum 25OHD level [17] whereas others find that vitamin D3 gives a larger increment [18]. We generally recommend that vitamin D3 be used when available. In some parts of the world, active metabolites are available for use in the treatment of osteoporosis. These metabolites are not a substitute for adequate vitamin D intake. Vitamin D is the substrate for 25OHD and the circulating 25OHD level may be important to support the non-renal production of 1,25-dihydroxyvitamin D. Local production of 1,25-dihydroxyvitamin D appears to mediate some of the non-classical effects of vitamin D.
Recommendations
The estimated average vitamin D requirement for older adults to reach a serum 25OHD level of 75 nmol/L (30 ng/ml) is 20 to 25 µg/day (800 to 1,000 IU/day). Considerably higher doses would be needed to ensure that almost all older adults reached 75 nmol/l (30 ng/ml). Efficacy of doses higher than 20 µg/day (800 IU/day) for fractures and 25 µg/day (1,000 IU/day) for falls however have not been evaluated in RCTs. It is therefore premature to recommend higher intakes for all older adults at this time.
The repletion dose will vary among individuals according to their starting level, their BMI, their effective sun exposure, and other unidentified factors. An intake lower than 20 µg/day (800 IU/day) may be adequate for individuals with regular effective sun exposure. Intake may need to be adjusted upward to as much as 50 µg/day (2,000 IU/day) in individuals who are obese, and in those with osteoporosis, limited sun exposure (institutionalized, homebound), and malabsorption, and in non-European populations known to be at high risk for vitamin D deficiency such as those in the Middle East and South Asia, or immigrants from such regions living in Europe. In these and other high-risk individuals, we recommend measuring the serum 25OHD level. The required dose to reach 75 nmol/L can be estimated from the measured level. Each 2.5 µg (100 IU) of added vitamin D will increase the serum 25OHD level by about 2.5 nmol/L (range 1.75-2.75 nmol/L) or 1.0 ng/ml (range 0.7 to 1.1 ng/ml) [2]. Because of the variability in individual 25OHD responses to supplemental vitamin D, however, in high-risk individuals, the serum 25OHD levels should be retested after about 3 months of supplementation to confirm that the target 25OHD level has been reached.
Conflicts of interest
None.
References
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2. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ (2003) Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204-210
3. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72:690-693 [erratum appears in Am J Clin Nutr. 2003 May;77(5):1342]
4. Blum M, Dallal GE, Dawson-Hughes B (2008) Body size and serum 25 hydroxy vitamin D response to oral supplements in healthy older adults. J Am Coll Nutr 27:274-279
5. Harris SS, Dawson-Hughes B (1998) The association of oral contraceptive use with plasma 25-hydroxyvitamin D levels. J Am Coll Nutr 17:282-284
6. Harris SS, Dawson-Hughes B (2002) Plasma vitamin D and 25OHD responses of young and old men to supplementation with vitamin D3. J Am Coll Nutr 21:357-362
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8. Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P (2007) 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 92:1415-1423
9. May W, Parris R, Beck C, Fassett J, Greenberg R, Guenther F, Kramer G, Wise S, Gills T, Colbert J, Gettings R, MacDonald B (2000) Definitions of terms and modes used at NIST for value-assignment of reference materials for chemical measurements. In Technology NIoSa (ed). US Government Printing Office, Gaithersburg
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11. Visser M, Deeg DJ, Lips P (2003) Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab 88:5766-5772
12. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav EJ, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. Br Med J 339:b3692
13. Ooms ME, Roos JC, Bezemer PD, van der Vijgh WJ, Bouter LM, Lips P (1995) Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. J Clin Endocrinolol Metab 80:1052-1058
14. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B (2005) Fracture prevention by vitamin D supplementation: a meta-analysis of randomized controlled trials. J Am Med Assoc 293:2257-2264
15. Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson-Hughes B, Eisman JA, El-Hajj Fuleihan G, Josse RG, Lips P, Morales-Torres J (2009) Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int 20:1807-1820
16. El-Hajj Fuleihan G (2009) Vitamin D deficiency in the Middle East and its health consequences. Clin Rev Bone Miner Metab 7:77-93
17. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD (2008) Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 93:677-681
18. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R (1998) Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 68:854-858
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