Chapter 13

Vitamin D and the Elderly Orthopedic Patient

Gerrit Steffen Maier1, Andreas Alois Kurth3, Konstantin Horas2, Kristina Kolbow1, Jörn Bengt Seeger4, Klaus Edgar Roth5, Djordje Lazovic1 and Uwe Maus1,    1Carl-von-Ossietzky-University, Oldenburg, Germany,    2Julius-Maxilians-University, Würzburg, Germany,    3Themistocles Gluck Hospital, Ratingen, Germany,    4Justus-Liebig-University, Giessen, Germany,    5Johannes-Gutenberg-University, Mainz, Germany


Vitamin D is a key player in calcium homeostasis and bone health. Beyond these well-known effects, new data suggest that vitamin D deficiency potentiates a variety of chronic disease states, including diabetes, cancer, and depression. Extremely low vitamin D levels have been associated with osteomalacia and impaired muscle function, both core elements in the field of orthopedic surgery. Good muscle function and healthy bones are essential for fast rehabilitation and positive outcome after orthopedic surgery as well, especially for elderly patients seeking good physical function. Physical function is important for the preservation of independence in daily life and for the prevention of falls, which are associated with fractures and high mortality.

This review focuses on the role of vitamin D deficiency in elderly orthopedic patients.


Vitamin D; hypovitaminosis D; sarcopenia; fracture prevention


Vitamin D is a key player in calcium homeostasis and bone health. Beyond these well-known effects, new data suggest that vitamin D deficiency potentiates a variety of chronic disease states, including diabetes, cancer, and depression. Extremely low vitamin D levels have been associated with osteomalacia and impaired muscle function, both core elements in the field of orthopedic surgery. Good muscle function and healthy bones are essential for fast rehabilitation and positive outcome after orthopedic surgery as well, especially in elderly patients seeking a return to good physical functioning. Physical function is important for the preservation of independence in daily life and for the prevention of falls, which are associated with fractures and high mortality. This review focuses on the role of vitamin D deficiency in elderly orthopedic patients.

Vitamin D

Vitamin D is a fat-soluble, secosteroid hormone required for proper regulation of many body systems and normal human growth and development (Hoffmann et al., 2015). Two common forms exist: vitamins D2 (ergocalciferol) and D3 (cholecalciferol). Vitamin D uptake or acquisition is regulated both through nutritional means (10–20%) and by the intradermal synthesis under the action of sunlight (80–90%). The main circulation form is 25-hydroxyvitamin D (25(OH)2D), the result of hydroxylation in the liver of vitamin D2 or D3. It is yielded into the biologically active form of vitamin D, calcitriol, or 1,25(OH)2D, through hydroxylation in the kidney. The active 1,25(OH)2D acts through specific vitamin D receptors to regulate calcium metabolism, differentiation, and division of various cell types (Holick and DeLuca, 1974).

The major source of vitamin D for most people is casual exposure of the skin to sunlight (Godar et al., 2011). When the precursor, 7-dehydrocholesterol, is exposed to ultraviolet light, it converts to previtamin D3 (Baggerly et al., 2015). Previtamin D3 undergoes nonenzymatic thermal transformation, which results in the production of vitamin D3 (Hoffmann et al., 2015). Due to the necessity of sun exposure and ultraviolet light, the endogenous synthesis can be affected by many different factors. Decreased synthesis of vitamin D can be attributed to high latitude, darker skin pigmentation, advanced age, and the use of sunblock and protective clothing (Adams et al., 1982; Clemens et al., 1982; Dowdy et al., 2010).

A limited number of foods naturally contain vitamin D, including fish, egg yolk, and offal such as liver. Because dietary intake of such foods is generally low in many countries, the use of supplements is important and should be recommended for groups prone to develop vitamin D deficiency such as infants and inactive elderly (Lips, 2007).

Vitamin D Status Assessment

Circulating 1,25-(OH)-D concentrations are under homeostatic control, limiting the value of 1,25-(OH)-D as a nutritional marker of vitamin D status (Hill et al., 2013). Serum concentrations closely reflect the amount of vitamin D synthesized in the skin and ingested in the diet. For this reason, 25-OH-D is widely accepted as a good biomarker of vitamin D status (Hill et al., 2013). During winter months in countries with a geographies above 40 degrees northern or southern latitude, the skin is not capable of synthesizing vitamin D for as long as 4–5 months (Webb et al., 1988). Therefore, it is assumed that during winter the circulating 25-OH-D levels are related to late-summer concentrations, oral intake, and body stores (Hill et al., 2013).

Vitamin D Deficiency

Vitamin D status has been studied on all continents and in most countries of the world (van Schoor and Lips, 2011). The best determinant of the serum vitamin D status is the serum concentration of 25-hydroxyvitamin D (25-OH-D) (Lips, 2001). As yet, there is no consensus on what constitutes normal vitamin D levels (Perez-Lopez et al., 2011). Many studies suggest 30 ng/mL as an optimal level, whereas others suggest 40 ng/mL, especially under particular conditions such as cancer involvement (Grant et al., 2009). The Institute of Medicine of the US National Academies has recommended an increase in minimal daily requirements for vitamin D and also raised its recommendation of an upper limit on a safe dose of vitamin D to 4000 international units (IUs) per day (Perez-Lopez et al., 2011). The US Endocrine Society guideline defines vitamin D deficiency as a serum 25-OH-D level less than 20 ng/mL (50 nmol/L) and vitamin D insufficiency as 25-OH-D values between 21 and 29 ng/mL (Pramyothin and Holick, 2012).

Hypovitaminosis D has been described in several studies in numerous segments of the global population. It is estimated to affect more than 1 billion people of all races, age groups, and ethnic backgrounds (Mithal et al., 2009). High rates of vitamin D deficiency in particular have been described among the elderly. One British study revealed a lower vitamin D level in people 65 and older than in the general public (Glowacki et al., 2003; Hirani and Primatesta, 2005). In postmenopausal American women taking antiosteoporotic medicine, more than 50% showed inadequate low vitamin D levels (Glowacki et al., 2003). Even young and healthy cohorts are at risk of developing hypovitaminosis D. In an American study from 2004, 52% of Boston-based adolescents of Hispanic and African American origin were suffering from hypovitaminosis D (Gordon et al., 2004).

Data on vitamin D status among the German population frequently reveals low vitamin D levels. In 14,000 individuals between one and 79 years of age, 62% of adolescent boys, 64% of adolescent girls, 57% of men, and 58% of women demonstrated vitamin D levels below 20 ng/mL (Hintzpeter et al., 2008). A study of 1578 elderly care rehabilitation facility patients in Germany published in 2012 showed severe vitamin D deficiencies with values below 10 ng/mL in 68% of patients. Only 4% of the patients had levels in the target range of 30–60 ng/mL (Schilling, 2012).

Among inpatients of geriatric acute care units, lower vitamin D serum levels have been associated with a greater severity of chronic diseases, increased risks of acute decompensation, and a higher risk of in-hospital mortality (Annweiler et al., 2010; Beauchet et al., 2012; Sutra Del Galy et al., 2009). In line with this, hypovitaminosis D doubled the risk of hospitalization for more than 14 days in a geriatric acute care unit (Beauchet et al., 2013).

Although several studies reported a widespread rate of vitamin D deficiency, epidemic data on elderly orthopedic patients is scarce. Data revealing the prevalence of vitamin D insufficiency and deficiency in elderly patients may be of value for treating orthopedic surgeons and geriatricians to prevent potential negative consequences in the operative and postoperative settings to maintain good physical function and to preserve independence in daily life. We reported in 2013 on an association between hypovitaminosis D and elderly orthopedic patients in general and found a high prevalence of vitamin D deficiency and insufficiency in such patients in an orthopedic department in central Germany (Maier et al., 2015a; Sutra Del Galy et al., 2009). We were able to show not only that orthopedic patients with hip or vertebral fractures have low vitamin D levels but also that elderly orthopedic patients in general had such low levels. A novelty in this study was that mainly nonhospitalized elderly patients were tested. Extremely low vitamin D levels have been associated with osteomalacia and impaired muscle function, both core elements in the field of orthopedic surgery. Good muscle function and healthy bones are essential for fast rehabilitation and positive outcome after orthopedic surgery as well as good physical function, especially in elderly patients (LeBoff et al., 2008; Maier et al., 2013a).

Physical function is important for the preservation of independence in daily life and for the prevention of falls, which are associated with fractures and high mortality (Annweiler et al., 2010; Bischoff-Ferrari et al., 2005; Bruyere et al., 2007). Vitamin D depletion has been linked with impaired cognition and specific damage to executive functions and speed of information processing, which can directly impact the selection of postural control strategies and reaction to falls (Annweiler and Beauchet, 2015; Annweiler et al., 2010). Low vitamin D levels negatively affect muscle strength, which may impact fall patterns, their severity, and reaction to them (Hamilton, 2010). Furthermore, several studies showed that lower 25-OH-D serum levels are a risk factor for orthostatic hypotension, which was reported to deteriorate the functional autonomy of older patients and to have a close relation with mortality and morbidity in the elderly (McCarroll et al., 2012; Soysal et al., 2014). In a study of 546 elderly patients aged 65 and older, vitamin D deficiency was shown to be a factor in the development of orthostatic hypotension. The authors concluded that during the evaluation of orthostatic hypotension serum, 25-OH-D levels should be checked and detected deficiencies should be treated (Soysal et al., 2014).

Vitamin D and Fracture Prevention

Vitamin D plays a pivotal role in bone mineralization. Vitamin D deficiency results in decreased bone mineralization as well as secondary hyperparathyroidism and increased cortical bone loss. In certain cases, severe vitamin D deficiencies can lead to osteomalacia. An autopsy study of deceased with clinically healthy bones found histopathological signs of osteomalacia with vitamin D levels below 30 ng/mL in 25% of all bone samples taken. Of note, samples with correlating vitamin D levels above 30 ng/mL did not show any signs of bone pathology (Priemel et al., 2010).

The relationship between vitamin D status and osteoporosis is of growing interest. Vitamin D levels below 20 ng/mL lead to malabsorption of intestinal calcium, and osteomalacia in the elderly as well as rickets in children (Holick, 2007; Lips, 2001). Several studies revealed that vitamin D status influences various outcomes of osteoporosis (Dawson-Hughes et al., 2005; Nakamura et al., 2011). One serious outcome of osteoporosis is fracture. Hip fractures are one of the most common fractures of the elderly (Maier et al., 2013b). Recent studies suggest that measurement of vitamin D serum concentrations might serve as a biomarker for hip-fracture risks among elderly patients (LeBoff et al., 1999; Lopes et al., 2009; Nuti et al., 2004). Current studies have shown a widespread rate of vitamin D deficiency in women with hip fractures (Dhanwal et al., 2010; Nurmi et al., 2005). These fractures contribute significantly to morbidity and mortality of elderly. As many as 50% of seniors will have permanent functional disabilities after hip fractures, and as many as 20% will die within the first year after the primary event (Bischoff-Ferrari et al., 2008). Supplementation of vitamin D has been shown to reduce the risk of falls (Bischoff-Ferrari et al., 2009a) and hip fractures (Bischoff-Ferrari et al., 2012). One of the first randomized controlled trials investigating the efficacy of vitamin D supplementation to prevent fractures compared the effect of 1200 mg of calcium and 20 μg vitamin D daily versus placebos in 3270 French women averaging 84 years of age. Under supplementation, bone mineral density increased and the risk of hip and nonvertebral fractures was reduced (Chapuy and Meunier, 1996). The Randomized Evaluation of Calcium or Vitamin D (RECORD) study compared the effect of calcium and vitamin D, alone or in combination, and placebos in 5292 community-dwelling older women or men with low-trauma fractures. Over the 62-month follow-up, the authors found no difference in the incidence of hip fractures or other fracture types. A possible explanation for the missing effect of supplementation was found in the extremely poor compliance with supplementation, especially when this included daily calcium (Grant et al., 2005). The women’s health initiative study showed an improvement in bone mineral density with the combined supplementation of calcium and vitamin D. Among patients who were compliant with the supplementation scheme there was a significant reduction in the risk of hip fractures (Jackson et al., 2006). A meta-analysis by Bischoff-Ferrari et al. (2009b) suggested that after adjustment of the vitamin D dose the incidence of nonvertebral fractures decreased independently of additional calcium supplementation.

Vertebral fragility fractures are another common type of osteoporosis complication. So far, a distinct correlation between these fractures and vitamin D levels has been described (Cummings et al., 1998; El Maghraoui et al., 2012). Vertebral fractures have direct and indirect effects on quality of life with increased morbidity and mortality (Lyles et al., 1993). Several studies revealed a high rate of hypovitaminosis D in postmenopausal women with osteoporotic vertebral fractures (El Maghraoui et al., 2012; Sakuma et al., 2011). A recent study showed a possible role of vitamin D levels in the occurrence of postkyphoplasty-recurrent vertebral compression fractures in elderly patients undergoing kyphoplasty due to osteoporotic fractures (Zafeiris et al., 2012).

In one of our recent studies, we identified a 89% prevalence of hypovitaminosis D in patients with vertebral fractures. By comparison, a well-matched group of patients with back pain in the absence of fracture who were seen in the same geographical locale (Mainz, Germany, 50 degrees northern latitude) and around the same time of year had a hypovitaminosis D prevalence of 60%. The majority of patients presenting with back pain had low vitamin D levels, regardless of whether or not fractures were present (Maier et al., 2015b). Our results suggest that patients who present with a vertebral fragility fracture are significantly more likely to be vitamin D insufficient or even deficient in comparison to patients without vertebral fractures. These results are in line with the findings of former studies, revealing that higher serum concentrations of vitamin D contribute to healthy bone metabolism and prevent osteoporosis as well as osteoporotic fractures (Bischoff-Ferrari et al., 2006).

Several studies examined the association between fractures in postmenopausal women and low vitamin D levels. Nakamura et al. showed in their 6-year cohort study of 773 community-dwelling elderly Japanese women that patients with sufficient vitamin D concentrations (>71 nmol/L) had a 58% lower risk of developing osteoporotic fractures than those with insufficient serum vitamin D concentrations. They concluded that optimal serum levels of vitamin D could reduce fracture risk (Nakamura et al., 2011). Gerdhem et al. (2005) were able to show that women with serum vitamin D concentrations below 20 ng/mL were twice as likely to sustain osteoporotic fractures compared to women with vitamin D concentrations above this threshold. In 415 elderly Brazilian women assessed with vertebral fragility fracture, vitamin D insufficiency was found to be one of the most important influencing factors (Lopes et al., 2009). El Maghraoui et al. enrolled 178 menopausal Moroccan women in their cohort study to determine serum vitamin D status and assess the association of bone mineral density and vertebral fractures. A widespread rate of vitamin D insufficiency (85% of tested patients) and deficiency (52%) was found. Furthermore, hypovitaminosis D was identified as an independent risk factor for vertebral fractures in postmenopausal women (El Maghraoui et al., 2012).

There is a certain discrepancy in literature regarding the association of gender with vitamin D levels and osteoporosis. Some studies indicate that females have a higher risk to be vitamin D deficient than men (Cooper et al., 1992), but other data identified male sex as a risk factor (Guardia et al., 2008). This conflicting literature indicates that gender may not necessarily be of importance for vitamin D deficiency, which is supported by our data. Both males and females need to be monitored for hypovitaminosis D because both groups are at high risk.

We have shown a mean vitamin D level of 17.1 ng/mL among 1083 patients 70 and older (Maier et al., 2015a). Data on such old geriatric and orthopedic patients is scarce, but they all support a widespread rate of hypovitaminosis D in the elderly (Drinka, 1996). This is an alarming fact, knowing that the official recommendation by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis is a minimum serum 25-OH-D level of 30 ng/mL in fragile elderly subjects at an elevated risk of falls and fractures (Rizzoli et al., 2013). Bischoff-Ferrari et al. (2004) showed a 22% reduction in falls of patients taking vitamin D supplements. Gerdhem et al. (2005) evaluated 986 postmenopausal women and showed a twofold increased fracture risk for patients with 25-OH-D levels below 20 ng/mL compared to patients with higher serum vitamin D levels. Moreover, a contributing role of vitamin D deficiency in the occurrence of simultaneous fractures has recently been described in a study of 472 elderly hip fracture patients (Di Monaco et al., 2011).

Nonskeletal Effects of Vitamin D

Besides its regulatory function in bone metabolism, vitamin D has been found by several studies to exert a growing number of nonskeletal effects. In particular, hypovitaminosis D has been linked to a higher risk of cardiovascular diseases, type 2 diabetes, and even mental illness (Giovannucci et al., 2008; Mattila et al., 2007; Menkes et al., 2012). Furthermore, vitamin D also regulates innate and adaptive immune functions by activating macrophages, dendritic cells, and lymphocytes (Hewison, 2010). Hypovitaminosis D has been shown to increase the risk of respiratory tract infection and periprosthetic joint infection, and a recent clinical trial demonstrated that vitamin D supplementation decreases the risk of influenza A infection (Ginde et al., 2009; Maier et al., 2014; Urashima et al., 2010). Dobnig et al. (2008) showed in their prospective cohort study of 3258 patients that patients with deficient vitamin D levels were twice as likely to die over a 7-year follow-up than patients with normal serum 25-OH-D levels. Vitamin D levels below 17.8 ng/mL were shown to increase the risk of death by 26% of all mortalities in the general population. Matthews et al. showed an inverse relation with the length of hospital stay and vitamin D levels in surgical patients admitted to the intensive care unit. With more than 250 patients evaluated, the mean length of stay for patients with severe vitamin D deficiency (<13 ng/mL) was 13.33 days compared to 5.17 days for patients with vitamin D levels above 27 ng/mL (Matthews et al., 2012). The length of stay of 253 patients of a geriatric acute care unit was inversely associated with low vitamin D levels. Helard et al. (2013) reported that patients with vitamin D levels below 50 nmol/L were hospitalized 3 days longer on average than patients with vitamin D levels above 50 nmol/L. Thus, vitamin D not only is important to bone health but also plays an important role in immunomodulation, the regulation of inflammation and cytokines, cell proliferation, cell differentiation, apoptosis, angiogenesis, muscle strength, and muscle contraction.


1. Adams JS, Clemens TL, Parrish JA, Holick MF. Vitamin-D synthesis and metabolism after ultraviolet irradiation of normal and vitamin-D-deficient subjects. N Engl J Med. 1982;306:722–725.

2. Annweiler C, Beauchet O. Questioning vitamin D status of elderly fallers and nonfallers: a meta-analysis to address a ‘forgotten step’. J Intern Med. 2015;277:16–44.

3. Annweiler C, Montero-Odasso M, Schott AM, Berrut G, Fantino B, Beauchet O. Fall prevention and vitamin D in the elderly: an overview of the key role of the non-bone effects. J Neuroeng Rehabil. 2010;7:50.

4. Annweiler C, Pochic S, Fantino B, et al. Serum vitamin D concentration and short-term mortality among geriatric inpatients in acute care settings. Adv Ther. 2010;27:245–249.

5. Baggerly CA, Cuomo RE, French CB, et al. Sunlight and vitamin D: necessary for public health. J Am Coll Nutr. 2015;34:359–365.

6. Beauchet O, Helard L, Montero-Odasso M, de Decker L, Berrut G, Annweiler C. Hypovitaminosis D in geriatric inpatients: a marker of severity of chronic diseases. Aging Clin Exp Res. 2012;24:188–192.

7. Beauchet O, Launay CP, Maunoury F, de Decker L, Fantino B, Annweiler C. Association between vitamin D deficiency and long hospital stay in geriatric acute care unit: results from a pilot cohort study. Aging Clin Exp Res. 2013;25:107–109.

8. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al. Effect of Vitamin D on falls: a meta-analysis. JAMA. 2004;291:1999–2006.

9. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293:2257–2264.

10. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84:18–28.

11. Bischoff-Ferrari HA, Can U, Staehelin HB, et al. Severe vitamin D deficiency in Swiss hip fracture patients. Bone. 2008;42:597–602.

12. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009a;339:b3692.

13. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009b;169:551–561.

14. Bischoff-Ferrari HA, Willett WC, Orav EJ, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367:40–49.

15. Bruyere O, Malaise O, Neuprez A, Collette J, Reginster JY. Prevalence of vitamin D inadequacy in European postmenopausal women. Curr Med Res Opin. 2007;23:1939–1944.

16. Chapuy MC, Meunier PJ. Prevention of secondary hyperparathyroidism and hip fracture in elderly women with calcium and vitamin D3 supplements. Osteoporos Int. 1996;6(suppl. 3):60–63.

17. Clemens TL, Adams JS, Henderson SL, Holick MF. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet. 1982;1:74–76.

18. Cooper C, Campion G, Melton 3rd LJ. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992;2:285–289.

19. Cummings SR, Browner WS, Bauer D, et al. Endogenous hormones and the risk of hip and vertebral fractures among older women Study of Osteoporotic Fractures Research Group. N Engl J Med. 1998;339:733–738.

20. Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–716.

21. Dhanwal DK, Kochupillai N, Gupta N, Cooper C, Dennison EM. Hypovitaminosis D and bone mineral metabolism and bone density in hyperthyroidism. J Clin Densitom. 2010;13:462–466.

22. Di Monaco M, Vallero F, Castiglioni C, Di Monaco R, Tappero R. Low levels of 25-hydroxyvitamin D are associated with the occurrence of concomitant upper limb fractures in older women who sustain a fall-related fracture of the hip. Maturitas. 2011;68:79–82.

23. Dobnig H, Pilz S, Scharnagl H, et al. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008;168:1340–1349.

24. Dowdy JC, Sayre RM, Holick MF. Holick’s rule and vitamin D from sunlight. J Steroid Biochem Mol Biol. 2010;121:328–330.

25. Drinka P. Vitamin D deficiency in older people. J Am Geriatr Soc. 1996;44:333.

26. El Maghraoui A, Ouzzif Z, Mounach A, et al. Hypovitaminosis D and prevalent asymptomatic vertebral fractures in Moroccan postmenopausal women BMC. Womens Health. 2012;12:11.

27. Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K. Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporos Int. 2005;16:1425–1431.

28. Ginde AA, Mansbach JM, Camargo Jr CA. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169:384–390.

29. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168:1174–1180.

30. Glowacki J, Hurwitz S, Thornhill TS, Kelly M, LeBoff MS. Osteoporosis and vitamin-D deficiency among postmenopausal women with osteoarthritis undergoing total hip arthroplasty. J Bone Joint Surg Am. 2003;85-A:2371–2377.

31. Godar DE, Pope SJ, Grant WB, Holick MF. Solar UV doses of adult Americans and vitamin D(3) production. Dermatoendocrinology. 2011;3:243–250.

32. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004;158:531–537.

33. Grant AM, Avenell A, Campbell MK, 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;365:1621–1628.

34. Grant WB, Cross HS, Garland CF, et al. Estimated benefit of increased vitamin D status in reducing the economic burden of disease in western Europe. Prog Biophys Mol Biol. 2009;99:104–113.

35. Guardia G, Parikh N, Eskridge T, Phillips E, Divine G, Rao DS. Prevalence of vitamin D depletion among subjects seeking advice on osteoporosis: a five-year cross-sectional study with public health implications. Osteoporos Int. 2008;19:13–19.

36. Hamilton B. Vitamin D and human skeletal muscle. Scand J Med Sci Sports. 2010;20:182–190.

37. Helard L, Mateus-Hamdan L, Beauchet O, Annweiler C. Hypovitaminosis D in geriatric acute care unit: a biomarker of longer length of stay. Dis Markers. 2013;35:525–529.

38. Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am. 2010;39:365–379.

39. Hill TR, Aspray TJ, Francis RM. Vitamin D and bone health outcomes in older age. Proc Nutr Soc. 2013;72:372–380.

40. Hintzpeter B, Mensink GB, Thierfelder W, Muller MJ, Scheidt-Nave C. Vitamin D status and health correlates among German adults. Eur J Clin Nutr. 2008;62:1079–1089.

41. Hirani V, Primatesta P. Vitamin D concentrations among people aged 65 years and over living in private households and institutions in England: population survey. Age Ageing. 2005;34:485–491.

42. Hoffmann MR, Senior PA, Mager DR. Vitamin D supplementation and health-related quality of life: a systematic review of the literature. J Acad Nutr Diet. 2015;115:406–418.

43. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281.

44. Holick MF, DeLuca HF. Vitamin D metabolism. Ann Rev Med. 1974;25:349–367.

45. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354:669–683.

46. LeBoff MS, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowacki J. Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA. 1999;281:1505–1511.

47. LeBoff MS, Hawkes WG, Glowacki J, Yu-Yahiro J, Hurwitz S, Magaziner J. Vitamin D-deficiency and post-fracture changes in lower extremity function and falls in women with hip fractures. Osteoporos Int. 2008;19:1283–1290.

48. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev. 2001;22:477–501.

49. Lips P. Vitamin D status and nutrition in Europe and Asia. J Steroid Biochem Mol Biol. 2007;103:620–625.

50. Lopes JB, Danilevicius CF, Takayama L, et al. Vitamin D insufficiency: a risk factor to vertebral fractures in community-dwelling elderly women. Maturitas. 2009;64:218–222.

51. Lyles KW, Gold DT, Shipp KM, Pieper CF, Martinez S, Mulhausen PL. Association of osteoporotic vertebral compression fractures with impaired functional status. Am J Med. 1993;94:595–601.

52. Maier GS, Jakob P, Horas K, Roth KE, Kurth AA, Maus U. Vitamin D deficiency in orthopaedic patients: a single center analysis. Acta Orthop Belg. 2013a;79:587–591.

53. Maier S, Sidelnikov E, Dawson-Hughes B, et al. Before and after hip fracture, vitamin D deficiency may not be treated sufficiently. Osteoporos Int. 2013b;24:2765–2773.

54. Maier GS, Horas K, Seeger JB, Roth KE, Kurth AA, Maus U. Is there an association between periprosthetic joint infection and low vitamin D levels? Int Orthop. 2014;38:1499–1504.

55. Maier GS, Horas K, Seeger JB, Roth KE, Kurth AA, Maus U. Vitamin D insufficiency in the elderly orthopaedic patient: an epidemic phenomenon. Int Orthop. 2015a;39:787–792.

56. Maier GS, Seeger JB, Horas K, Roth KE, Kurth AA, Maus U. The prevalence of vitamin D deficiency in patients with vertebral fragility fractures. Bone Joint J. 2015b;97-B:89–93.

57. Matthews LR, Ahmed Y, Wilson KL, Griggs DD, Danner OK. Worsening severity of vitamin D deficiency is associated with increased length of stay, surgical intensive care unit cost, and mortality rate in surgical intensive care unit patients. Am J Surg. 2012;204:37–43.

58. Mattila C, Knekt P, Mannisto S, et al. Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care. 2007;30:2569–2570.

59. McCarroll KG, Robinson DJ, Coughlan A, Healy M, Kenny RA, Cunningham C. Vitamin D and orthostatic hypotension. Age Ageing. 2012;41:810–813.

60. Menkes DB, Lancaster K, Grant M, Marsh RW, Dean P, du Toit SA. Vitamin D status of psychiatric inpatients in New Zealand’s Waikato region. BMC Psychiatry. 2012;12:68.

61. Mithal A, Wahl DA, Bonjour JP, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009;20:1807–1820.

62. Nakamura K, Saito T, Oyama M, et al. Vitamin D sufficiency is associated with low incidence of limb and vertebral fractures in community-dwelling elderly Japanese women: the Muramatsu Study. Osteoporos Int. 2011;22:97–103.

63. Nurmi I, Kaukonen JP, Luthje P, et al. Half of the patients with an acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland. Osteoporos Int. 2005;16:2018–2024.

64. Nuti R, Martini G, Valenti R, et al. Vitamin D status and bone turnover in women with acute hip fracture. Clin Orthop Relat Res. 2004;208–213.

65. Perez-Lopez FR, Chedraui P, Fernandez-Alonso AM. Vitamin D and aging: beyond calcium and bone metabolism. Maturitas. 2011;69:27–36.

66. Pramyothin P, Holick MF. Vitamin D supplementation: guidelines and evidence for subclinical deficiency. Curr Opin Gastroenterol. 2012;28:139–150.

67. Priemel M, von Domarus C, Klatte TO, et al. Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res. 2010;25:305–312.

68. Rizzoli R, Boonen S, Brandi ML, et al. Vitamin D supplementation in elderly or postmenopausal women: a 2013 update of the 2008 recommendations from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Curr Med Res Opin. 2010;29:305–313.

69. Sakuma M, Endo N, Hagino H, et al. Serum 25-hydroxyvitamin D status in hip and spine-fracture patients in Japan. J Orthop Sci. 2011;16:418–423.

70. Schilling S. Epidemic vitamin D deficiency among patients in an elderly care rehabilitation facility. Dtsch Arztebl Int. 2012;109:33–38.

71. Soysal P, Yay A, Isik AT. Does vitamin D deficiency increase orthostatic hypotension risk in the elderly patients? Arch Gerontol Geriatr. 2014;59:74–77.

72. Sutra Del Galy, Bertrand A, Bigot M, et al. Vitamin D insufficiency and acute care in geriatric inpatients. J Am Geriatr Soc. 2009;57:1721–1723.

73. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010;91:1255–1260.

74. van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab. 2011;25:671–680.

75. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab. 1988;67:373–378.

76. Zafeiris CP, Lyritis GP, Papaioannou NA, et al. Hypovitaminosis D as a risk factor of subsequent vertebral fractures after kyphoplasty. Spine J. 2012;12:304–312.

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