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4612-4621-Vitamin D Supplementation for Osteoporosis in Older Adults: Can We Make It Help Better?

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4612-4621-Vitamin D Supplementation for Osteoporosis in Older Adults: Can We Make It Help Better? Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2016; 20: 4612-4621 Vitamin D supplementation for osteoporosis in older adults: can we make it help better? C.-H. DONG 1,2 , Q.-M. GAO 1, Z.-M. WANG 2, A.-M. WANG 2, P. ZHEN 1 1The Center of Orthopaedic Surgery of PLA, the General Hospital of Lanzhou Military Command, Gansu, China 2Department of Orthopedics, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China Abstract. – With the increase of the average such diseases is osteoporosis. The true incidence age of our population, the incidence of diseases of osteoporosis, the disease of weakened bones specific for older adults has been increasing. One of such diseases is osteoporosis. The true that causes heightened risk of bone fractures, is incidence of osteoporosis is unknown. But the unknown. But the estimates indicate that this dis - estimates indicate that this disease affects wide ease affects wide proportions of the population, proportions of the population, ranging in mil - ranging in millions or even ten millions in large lions or even ten millions in large countries like countries like the United States. As this poses a the United States. As this poses a significant burden on the health care system, interventions significant burden on the health care system, in - that could prevent or treat this condition are in terventions that could prevent or treat this condi - the focus of clinical research. Vitamin D, the de - tion are in the focus of clinical research. Vitamin terminant of bone health, has been tested in clin - D, the determinant of bone health, has been test - ical studies as the agent to treat osteoporosis. ed in clinical studies as the agent to treat osteo - Despite the progress, there is still some contro - porosis. Despite the progress, there is still some versy about the targeted blood levels of vitamin D, most efficient way to supplement this vitamin, controversy about the targeted blood levels of vi - and clinical efficacy of this supplementation in tamin D, most efficient way to supplement this the elderly. vitamin, and clinical efficacy of this supplemen - In the present review, we will highlight the me - tation in the elderly. In the present review, we tabolism of vitamin D and the aforementioned will highlight the metabolism of vitamin D and unresolved issues, as well as review the recent the aforementioned unresolved issues, as well as interventional studies on vitamin D supplemen - tation. review the recent interventional studies on vita - min D supplementation . Key Words: Elderly, Osteoporosis, Vitamin D, Supplementation, The Metabolism of Vitamin D Guidelines, Analysis, Biochemistry, Metabolism, Clini - Vitamin D is classified as a fat-soluble vita - cal efficacy . min, although the chemical structure of its bio - logically active metabolite is actually close to steroid hormones . Another similarity between the Introduction biologically active metabolite and steroid hor - mones is that both these compounds bind to spe - With industrialization and urbanization of in - cialized receptors to exert their biological effects. creasing number of countries in the world, life We will address this metabolite in a few para - expectancy increases, and so does the relative graphs below. proportion of older adults. The definition of “old - Humans maintain the circulating levels of vita - er adults ”, or the “elderly”, differs depending on min D mainly through exposure of our skin to the the country (http://www.who.int/healthinfo/sur - ultraviolet light during sunny days. At higher lati - vey/ageingdefnolder/en/ ), and most industrialized tudes, vitamin D production occurs mostly dur - countries consider the population at the age of 65 ing warm seasons, probably due to the quantity years or older as “older adults”. Our longer life and quality of sun’s ultraviolet light reaching the expectancy has also brought about several age- surface 1. Minor contributors to circulating levels related diseases and conditions that had been rel - of vitamin D are dietary sources (such as cod liv - atively rare in pre-industrialized ages. One of er oil, fish, and milk supplemented with vitamin 4612 Corresponding Author: Ping Zhen, MD; e-mail: [email protected] Vitamin D supplementation for osteoporosis in older adults: can we make it help better? D). Recommendations have been introduced that is called vitamin D 2 (ergocalciferol). Both D 3 and vitamin D supplements should also be recog - D2 forms of vitamin D can be equally well me - nized as one of the sources, especially for popu - tabolized in our body 4. The experts often use the lations at increased risk for osteoporosis, includ - term “vitamin D” interchangeably , referring to 2 4,5 ing the elderly . Therefore, pharmaceutical sup - D3 or D 2 . Oral supplementation can be done plements have become another determinant of with either plant-based or animal metabolites of the circulating vitamin D levels. vitamin D . When our skin is exposed to the sun, some of After it is produced in the skin, vitamin D 3 (or the ultraviolet light is absorbed by melanin, the D2) is further metabolized in the liver, or can be skin pigment. Therefore, people with darker skin stored in the fat tissue 5 to be released into the need longer exposure to the sun than people with blood stream when needed, thereby repleting the fair skin to achieve similar levels of the circulat - levels . In the liver, vitamin D 3 passes through hy - ing vitamin D 3. The ultraviolet light catalyzes a droxylation 5. This process yields the circulating chemical reaction in the skin that produces vita - vitamin D metabolite called 25-hydroxyvitamin 4 min D from 7-dehydrocholesterol . The form of D3 (Figure 1). It will be highlighted in the subse - vitamin D produced in our skin or in animals is quent text that 25-hydroxyvitamin D 3 is the cur - referred to as vitamin D 3 (or cholecalciferol; Fig - rent indicator of our body’s vitamin D status ure 1 ), whereas its counterpart produced in plants quantified in hospital labs . Notably, clinical rec - Figure 1. Metabolism of vitamin D. The skin produces the preform of vitamin D (cholecalciferol) from 7-dehydrocholesterol. After it is produced in the skin, cholecalciferol is hydroxylated in the liver to yield 25-hydroxyvitamin D3. 25-hydroxyvitamin D3 is the most abundant circulating form of vitamin D in the human body. 25-hydroxyvitamin D3 circulates in blood mostly bound to the transporting protein (vitamin D binding protein). A very small fraction of 25-hydroxyvitamin D3 is bound to serum albumin or is free. In kidney and other organs, 25-hydroxyvitamin D3 is further hydroxylated to produce the biological - ly active 1,25-dihydroxyvitamin D3. The latter vitamin D metabolite in the target organs activates the vitamin D receptor (VDR) which up-regulates transcription of a large group of genes, called “vitamin D-responsive genes”. 4613 C.-H. Dong, Q.-M. Gao, Z.-M. Wang, A.-M. Wang, P. Zhen ommendations for healthy and diseased bone me - els of 25-hydroxyvitamin D 3 to maintain suffi - tabolism have been developed around this cient circulating and intracellular levels of 1,25- metabolite. dihydroxyvitamin D 3. This is why it is important First, the circulating levels of 25-hydroxyvita - that the levels of 25-hydroxyvitamin D 3 are suffi - min D 3 are considered stable, with a half-life of ciently high, and this will be addressed in the about two weeks 6 or even longer 7. Thus, these subsequent text . levels are not the subject to diurnal or between- days variations, and newest reports suggest that Analytical Issues muscle tissue can be the body’s storage site for There are several reasons why 25-hydroxyvita - 8 25-hydroxyvitamin D 3 . Thereby, our body ap - min D 3 is still considered the indicator of the pears to have at least two storage tissues: fat tis - body’s vitamin D status. sue to store vitamin D 3 and muscle tissue for 25- First, the serum concentration of 25-hydrox - hydroxyvitamin D 3 storage. It is possible that for yvitamin D 3 is much higher than that of 1,25-di - this reason, our body maintains healthy levels of hydroxyvitamin D 3, which makes it less chal - 25-hydroxyvitamin D 3 long after begin of the lenging to develop an analytical assay. The sec - cold season. ond reason is the much shorter lifespan 1,25-di - 25-hydroxyvitamin D 3 circulates in blood hydroxyvitamin D 3 and fluctuation of its levels . mostly bound to the transporting protein (vitamin Obviously, an indicator should be stable under D binding protein). A very small fraction of 25- similar bodily conditions, and this is not the case hydroxyvitamin D 3 is bound to serum albumin or with 1,25-dihydroxyvitamin D 3. 9 is free . In the kidney, 25-hydroxyvitamin D 3 is However, this does not mean that the analyti - further metabolized to produce the biologically cal tests for 25-hydroxyvitamin D 3 are problem- active 1,25-dihydroxyvitamin D 3 (Figure 1). free. There is a discrepancy between analytical While the kidney is considered the major conver - assays from different suppliers. Furthermore, sion site from 25-hydroxyvitamin D 3 to 1,25-di - some assays report total 25-hydroxyvitamin D 5 hydroxyvitamin D 3 , this conversion is also (i.e. the sum of 25-hydroxyvitamin D 3 and 25- 4 thought to occur in other tissues . The latter vita - hydroxyvitamin D 2), whereas other assays pro - min D metabolite activates the vitamin D recep - vide information on these two metabolites sepa - tor (Figure 1) which modulates transcription of a rately. For consistency reasons, the guidelines large group of genes, called “vitamin D-respon - recommend reporting total 25-hydroxyvitamin D sive genes” (or “vitamin D-sensitive genes”) levels, as this will be applicable to the patients (Figure 1).
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