Effects and Interactions of Vitamin D Deficiency, Calcium and Parathyroid Hormone on Physical Concerns in the Elderly: A Review, The
Vitamin D, calcium, and parathyroid hormone function together in a tightly regulated system: alterations in the level of one of these chemicals has significant effects on the levels of the other two. Systems and/or functions that may be affected by improper levels of one or all of these elements include bone formation, blood pressure regulation, glucose tolerance, muscle contraction and strength, and balance and falls. This paper reviews the physiology of maintenance of proper levels of these elements and discusses pathologies associated with the cycle of vitamin D deficiency, specifically as they relate to concerns of the physical therapist working with the geriatric population. Suggestions for proper dietary levels will be discussed as well as prophylactic recommendations to prevent pathological conditions.
Key Words: physical therapy, nutrition, osteoporosis
The human aging process includes many changes in the synthesis and metabolism of several chemical elements within the body. In addition, physical inactivity, changes in diet, and medication use, which are common in geriatric populations, often compound aging systems problems.1 For example, alterations in vitamin intake, digestion, and absorption can potentially affect cognition and mobility, functions of concern to physical therapists working with this population.
Vitamin D is a nutrient important in the metabolism of bone. However, research demonstrates that vitamin D nutriture in most older adults is poor.The purpose of this paper is to provide a review for physical therapists on the role of vitamin D in calcium metabolism, parathyroid function,and bone health. An additional goal is to discuss pathologies and impairments associated with the’cycle of vitamin D deficiency’ as they relate to physical therapy concerns. The review will conclude by addressing the role of physical therapy and provide recommendations for practice.
A Medline search was performed in December 2002 and June 2003 using primarily the search terms Vitamin D and muscle weakness/Vitamin D and falls/’vitamin D and osteoporosis/ and ‘vitamin D and aging/ These subtopics were culled from an original source by Lips.2 Titles and abstracts were reviewed and appropriate articles for inclusion were selected. Then, specific searches, smaller in scope, were conducted to clarify topical areas of the review. Recent articles were preferred and older manuscripts were sought only for clarification and foundational information.
PHYSIOLOGY OF VITAMIN D
Vitamin D is a hormone that enhances the absorption of calcium and phosphate in the gut to facilitate the mineralization of bone. Sources of vitamin D include a cycle begun by exposure to sunshine or ultraviolet (UV) irradiation of the skin, dietary intake, oral supplements, and injections.23 The synthesis of vitamin Din human skin begins with exposure to sunlight (UV). At that time, 7-dehydrocholesterol is converted to vitamin D^sub 3^. Vitamin D binding protein binds vitamin D and its metabolites for travel through the bloodstream until it reaches the liver, where it is hydroxylated into 25-hydroxyvitamin D (25-(OH)D). Further hydroxylation occurs in the kidney to make the conversion to 1,25 dihydroxyvitamin D (1,25-(OH)^sub 2^D), a steroid hormone.4 This conversion in the kidney is stimulated by parathyroid hormone (PTH), and it is the metabolite 1,25-(OH)^sub 2^D which is primarily responsible for the absorption of calcium and phosphate from the intestines.2 This cycle is based on a negative feedback loop. Thus, when calcium and phosphate blood levels are adequate, synthesis of 1,25-(OH)^sub 2^D in the kidney is slowed to maintain proper calcium homeostasis.2,5 High serum calcium levels cause a decrease in the secretion of PTH, leading to a decreased production of 1,25-(OH)^sub 2^D in the kidneys. Therefore, 1,25-(OH)^sub 2^D’s action on bone mineralization, and other processes, is indirect through the stimulation of enhanced calcium absorption from the intestinal lumen into the bloodstream.2 (Figure 1).
Dietary vitamin D supplementation of 400-800IU/d causes a cycle similar to naturally occurring vitamin D: there is an increase in serum 25 (OH)D, a decrease in serum PTH, a decrease in bone resorption, and changes in bone mass.2
PHYSIOLOGY OF CALCIUM
Calcium’s absorption from the gut is important for the maintenance of many physiological systems. In fact, the quantity of calcium required to preserve homeostasis and organ function is higher than that of any other mineral in the body.3 Approximately 99% of the calcium in the body is found in the teeth and bones and the other 1% is found in the blood and soft tissues.6
The mineral component of bone consists primarily of hydroxyapatite crystals, which are composed of 40% calcium and 60% phosphorus.6 The process of bone formation and resorption is continual, but there are age-associated changes in bone mineral content.The bone mineral content in cancellous bone actually begins resorption before the age of 20, and the resorption of cortical bone begins in the 30s. After menopause, the rate of bone mineral loss increases to 7% per year, with the greatest amount of loss occurring in the first 5 years of menopause.7 It has been estimated that there is approximately a 25% vertebral bone loss throughout life and 60% ofthat occurs within 10 years of menopause.8 In the state of osteoporosis, bone resorption exceeds formation. This occurs with lowered calcium levels in the body, or decreased absorption of serum calcium,6,9 which both serve to increase the release of PTH, which has a negative impact on bone density.7-10
Calcium is a necessary element for the vasoconstriction and vasodilation of blood vessels, and thus has a role in blood pressure regulation.6,11 The binding of calcium ions is necessary for the activation of vitamin K clotting factors to assist with coagulation.6 An additional role of calcium is in the maintenance of muscle contraction. Voltage-dependent calcium channels, as seen in nerve cells and skeletal muscle cells, require correct levels of calcium to maintain proper function. For example, in muscle contraction, the binding of calcium to troponin initiates the sliding and shortening of the muscle fibers. In addition, calcium must bind to the protein calmodulin in order to activate enzymes that break down glycogen and provide the energy required for muscle contraction.6
Calcium also is necessary for the release of several hormones, and the absorption of calcium is dependent upon adequate vitamin D levels.6 For example, researchers have noted that a decrease in vitamin D levels will reduce insulin secretion and the insulin response to glucose.2 Borissova and colleagues12 found that there was an increase in insulin secretion and a decrease in insulin resistance after one month of vitamin D3 supplementation. Similarly, Zitterman13 has noted improved glucose levels in subjects with diabetes after vitamin D supplementation.
PHYSIOLOGY OF OF PARATHYROID HORMONE
Parathyroid hormone plays a crucial role in the maintenance of both vitamin D and calcium levels in the body. When the levels of serum calcium decrease, calcium-sensing proteins in the parathyroid gland cause the secretion of PTH. Parathyroid hormone stimulates the conversion of vitamin D to calcitrol in the kidneys. Calcitrol, in turn, increases the luminal absorption of calcium. Together with PTH, calcitrol also stimulates the release of calcium from bone by the activation of osteoclasts and it causes an increase in calcium resorption in the kidneys. Parathyroid hormone levels also are based on a feedback loop; when serum calcium levels return to normal, PTH secretion ceases.6
Overall, calcium levels are very tightly and efficiently regulated. Ideally, dietary calcium should be adequate to meet the needs of all metabolic reactions requiring this element. However, when dietary intake of calcium is poor, the bony skeleton suffers by serving as a calcium source.6
Lack of vitamin D further compounds this problem. In cases of vitamin D deficiency or insufficiency, serum calcium levels are reduced and secondary hyperparathyroidism results in order to control against hypocalcemia.2’10 Interestingly, because vitamin D levels are affected by exposure to sunlight, secondary hyperparathyroidism has been shown to be more prevalent in the elderly at the end of the winter months and least prevalent at the end of the summer months, when more people are outdoors.14
Secondary hyperparathyroidism is believed to be the primary mechanism behind hip fractures.2 Excess PTH levels in primary hyperparathyroidism have been shown to have catabolic effects on cortical bone, eg, the femoral neck, but preserving effects on cancellous or trabecular bone.10’15 In a comprehensive review, Dempster and associates15 summarized numerous studies, with different populations, that have found that in the presence of excessive PTH, vertebral fractures are rare, whereas forearm and distal radial fractures are more common.
VITAMIN D DEFICIENCY AND PHYSICAL THERAPY CONCERNS
Vitamin D deficiency produces osteomalacia which is typified by an accumulation of unmineralized osteoid on bone surfaces. Researchers have shown an increase in osteomalacia associated with secondary hyperparathyroidism. secondary mineralization of osteoid tissue takes approximately 6 months, so the overall degree of mineralization is lower.2
Osteoporosis is characterized by a decrease in the total bone mass.2,5 Osteocalcin is a metabolic marker for bone activity, and is seen in higher concentrations when bone turnover is high. The synthesis of osteocalcin is induced by 1,25-(OH)2D in osteoblasts through a receptor complex. This receptor complex has genetically variant forms that are related to an increased rate of bone turnover in the elderly.5 This provides clues to the genetic susceptibility of certain individuals to osteoporosis.
There is an overwhelming amount of evidence to show that decreased levels of vitamin D and/or calcium affects bone mineral density.Ooms and colleagues16 found a positive correlation between serum 25-(OH)D levels and bone mineral density. A vitamin D intake level less than 100 ID/day was found to be associated with an increased risk for hip fracture.17 Another study cited a significantly decreased risk of hip fracture in elderly women who were taking vitamin D.18 Sato, et al19 found that vitamin D deficiency due to UV light deprivation and malnutrition, combined with secondary hyperparathyroidism, led to significant reductions in bone mineral density.
Vitamin D deficiency and altered calcium levels have also been associated with high blood pressure. Vascular smooth muscle is a target organ for vitamin D.” St John and associates20 demonstrated a significant relationship between blood pressure and calcitropic hormone levels in the elderly and concluded that hypertension may be linked to calcium deficiency. A meta-analysis performed on the role of supplemental calcium in the control of blood pressure revealed reductions in both systolic and diastolic pressures with 5002000 mg/day of supplemental calcium.6 Researchers have examined the effect of a diet rich in calcium as compared to one of fruits and vegetables and a control diet and showed that the calcium-enriched diet led to greater decreases in systolic blood pressure (11.4 mm Hg) and diastolic pressures (5.5 mm Hg) than the control diet.21,22 Pfeifer and colleagues11 investigated the effect of combined vitamin D and calcium therapy as compared to calcium alone in the reduction of systolic blood pressure, and found that the combined therapy led to a decrease in systolic blood pressure of 9.3% and a decrease in heart rate of 5.4% as compared to calcium alone. There were no significant differences in diastolic blood pressure levels. Pfeifer’s study was performed in the winter on subjects who had elevated PTH levels, thus demonstrating a hypovitaminosis state.
Salt intake also is related to calcium levels in the body, causing an increase in urinary excretion of calcium. In addition to contributing to elevated blood pressure, high salt intake has been linked to a higher rate of bone mineral loss in postmenopausal women. Because of its effect on calcium excretion, high salt intake has been linked to osteoporosis and fracture.11
Vitamin D deficiency also has been linked to muscle weakness. Through the mechanism of calcium-induced muscle contraction, a decrease in vitamin D and subsequent decrease in calcium levels can have a significant impact on muscle strength, muscle contractility, and function of the sarcoplasmic reticulum.23 Increases in muscle strength have been noted in patients treated surgically for primary hyperparathyroidism, suggesting that PTH excess may have an independent adverse affect on muscle function.23 Sato et al24 investigated the relationship between hip fracture, serum 25-(OH)D levels, and muscle fiber atrophy and found that the mean fiber diameter in Type Il muscle fibers of gluteus medius was significantly smaller in subjects with lower serum 25-(OH)D levels. The authors believed that these changes might weaken the support of the hip joint, predisposing these individuals to falls.24 Janssen and associates25 reported that vitamin D deficiency was associated with proximal muscle weakness. They noted that vitamin D metabolites can directly influence muscle cell maturation and functioning through a vitamin D receptor site. These researchers found that vitamin D supplementation in subjects who were elderly and vitamin D deficient helped to improve muscle strength and function and decrease falls. Similarly, Geusens et al26 demonstrated that differences in the gene for the vitamin D receptor in muscle were associated with differences in the strength of the quadriceps femoris muscle.
Levels of vitamin D and PTH may have effects on the neurological system as well, ultimately affecting balance and increasing risk of falls.There is support for the presence of a vitamin D receptor site in nervous tissue in animal studies. In the vitamin D-deficient rat, administration of 1,25-(OH)2D increased enzyme activity in brain tissue. Furthermore, parathyroid hormone has been shown to cross the blood brain barrier in humans, and there is an association between hyperparathyroidism and neurological disease.2′
Because of the effect of vitamin D deficiency and PTH on the neuromuscular system, the risk of falls warrants mention. Stein and colleagues23 investigated the relationship between falls and serum vitamin D and PTH levels, and found that ambulatory residents of a nursing home and hostel who fell had significantly lower levels of serum 25-(OH)D and significantly higher levels of PTH than residents who had never fallen. Those authors also reported that global vitamin D deficiency was best measured by 25-(OH)D levels rather than the shorter-lived 1,25-(OH)2D levels. Likewise, Pfeifer et al28 found that decreased vitamin D levels were associated with increased body sway and an elevated risk for falls and subsequent fracture in elderly women. Dhesi and colleagues29 found that older people who have fallen have impaired functional performance, psychomotor function, and muscle strength. Those subjects in the falls group who had the lowest levels of 25-(OH)D were the most severely affected. Lastly, Dhesi et al30 found that up to 72% of individuals in a falls clinic were found to have had an insufficiency of vitamin D.Those authors advocated providing clinic participants with vitamin D supplements because of the evidence linking vitamin D deficiency to increased falls and body sway.
IMPLICATION FOR PHYSICAL THERAPISTS
Maintenance of proper levels of vitamin D, calcium, and parathyroid hormone is important for many bodily systems of particular concern to physical therapists. As shown, improper levels can affect the muscular system, the skeletal system, and the nervous systems; there are functional and safety implications, as well. (Table 1). The physical therapist needs to be aware of these consequences and incorporate appropriate interventions into the treatment plan. Weightbearing activities and muscle strengthening can assist in the proper maintenance of bone mass. Proper levels of exercise can aid in maintaining proper glucose levels in the body and controlling against hypertension and balance impairments can be addressed through balance activities, strengthening of the ankle, and patient education for safety awareness.
DIETARY AND UV EXPOSURE RECOMMENDATIONS
There is evidence that the daily requirement for vitamin D increases with age.31 Currently, recommended dietary intake for vitamin D for people who are elderly is 400 lU/day/ Most people who are elderly do not engage in outdoor activity often/ and when they do, they might be wearing sunscreens, which will block the skin’s absorption of UV light.2 Because of this, their dietary intake needs to be higher than the standard recommendation.” Additionally, there is evidence to suggest that the skin of older individuals cannot synthesize vitamin D as effectively as the skin of younger people, and that the vitamin D that is produced is less readily absorbed in the intestine.2,4 Nevertheless, research has shown that 10 minutes of unprotected UV exposure 3 times per week is adequate to prevent vitamin D deficiency in the elderly. However, this amount will vary somewhat depending upon latitude and time of year. Vitamin D production has been shown to be significantly lower in the northern latitudes, specifically during the winter months.2
Dietary sources of vitamin D such as oily fish, eggs, liver, butter, and vitamin D-fortified milk improve vitamin D nutriture.3 Absorption of vitamin D in the elderly is usually adequate. However, some conditions such as celiac disease, can compromise absorption.2 Similarly, kidney or liver dysfunction can affect the hydroxylation of vitamin D, and the entire subsequent chain of events.
The recommended dietary intake level for the elderly for calcium is currently 1200-1500 mg/day.7 Major dietary sources of calcium are dairy products, tofu, sardines, broccoli, cabbage, Chinese cabbage, spinach, and collard greens.36 However, hyperparathyroidism is frequently seen in persons with gastrointestinal disease due to the malabsorption of calcium.This can lead to an increased production of 1,25-(OH)2D and subsequent depletion of vitamin D reserves.5 Treatment for gastrointestinal conditions can improve absorption of several minerals. It is important to note that there is an age-related decrease in calcium absorption, which may be as much as a 50%, partly due to a decrease in serum levels of 1,25(OH)2D.2,7
SUMMARY AND RECOMMENDATIONS
The interrelationship of vitamin D, calcium, and PTH has been shown to be tightly regulated. However, disruption in the balance of these elements can have significant effects on body function. Physical therapists need to be aware of the effects of these substances on mobility and on related body structures. In addition, they should become knowledgeable about the consequences of altered blood pressure, fracture, risk for falls, and neurological functioning as they relate to poor vitamin D and calcium nutriture. As part of the examination and rehabilitation process, therapists can question patients regarding their intake of calcium- and vitamin D-enhancing foods, about the use of dietary supplements, and whether they have a history of muscle weakness and/or falls. When vitamin D and calcium nutriture are in doubt,therapists could refer clients to a physician and/or a registered dietician for counseling and intervention. Regulation of calcium, vitamin D, and PTH levels can be readily accomplished through supplementation and consumption of an appropriate diet. Therefore, physical therapists treating older clients can contribute to these easy solutions by providing a thorough assessment and efficacious referral to other health professionals.
The author would like to thank Constance McCloy, PT, EdD, ATC for her assistance with revisions of this manuscript.
1. Guccione A, ed. Geriatrie Physical Therapy. 2nd ed. St. Louis, Mo: Mosby; 2000.
2. 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.
3. Ferrini AF, Ferrini RL. Nutrition. In: Health in the Later Years. 3rd ed. Boston, Mass: McGraw-Hill; 2000:120-164.
4. Marriott BM. Vitamin D supplementation: a word of caution. Annlnt Med. 1997; 127:231-233.
5. Fraser DR.Vitamin D. Lancet 1995; 345:104-107.
6. Calcium. Available at: http://osu.orst.edu/dept/lpi/info center/minerals/calcium/calcium.html. Accessed December 8,2002.
7. Bottomley J. Age-related bone health and pathophysiology of osteoporosis. Orthop Phys Ther CUn N Amer. 1998; 7: 117-132.
8. Geusens P, Dequeker J, Verstraeten A, NiJs J. Age-, -sex-, and menopause-related changes of vertebral and peripheral bone: population study using dual and single photon absorptiometry and radiogrammetry.J/Vuc//Wec/. 1986; 27:1540-1549.
9. Papaioannou A, Watts NB, Kendler DL,Yuen CK, Adachi JD, Ferko N. Diagnosis and management of vertebral fractures in elderly adults. Am J Med. 2002;113:220-228.
10. Rubin MR, Bilezikian JP.The role of parathyroid hormone in the pathogenesis of glucocorticoid-induced osteoporosis: a reexamination of the evidence. J Clin Endocrinol Metob. 2002; 87:4033-4041.
11. Pfeifer M, Begerow B, Helmut W, Nachtigall D, Hansen C. Effects of a short-term vitamin D3 and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab. 2001; 86: 1633-1637.
12. Borissova AM,Tankova T, Kirilov G, Dakofka L, Kovacheva R. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. lnt J CUn Pract. 2003; 57:258-261.
13. Zitterman A.Vitamin D in preventive medicine: are we ignoring the evidence? BrJNutr. 2003; 89:552-572.
14. Lips P, Hackeng WHL, Jongen MJM, van Ginkel FC, Netelenbos JC. Seasonal variation in serum concentrations of parathyroid hormone in elderly people. J Clin Endocrinol Metab. 1983; 57:204-206.
15. Dempster D, Cosman F, Parisien M, Shen V, Lindsay R. Anabolic actions of parathyroid hormone on bone. Endocr Rev. 1993; 14:690-709.
16. Ooms ME, Lips P, Roos JC, et al. Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women. J Bone Miner Res. 1995; 10:1177-1184.
17. Meyer H E, Henriksen C, Falch JA, Pedersen Jl,Tverdal A. Risk factors for hip fracture in a high incidence area: a case control study from Oslo, Norway. Osteoporosis Int. 1995; 5:239-246.
18. Ranstam J, Kanis JA. Influence of age and body mass on the effects of vitamin D on hip fracture risk. Osteoporosis Int. 1995;5:450-454.
19. Sato Y, Asoh T, Oizumo K. High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer’s disease. Bone. 1998;23:555-557.
20. St. John A, Dick I, Hoad K, Retallack R, Welborn T. Relationship between calcitrophic hormones and blood pressure in elderly subjects. Eur J Endocrinol. 1994;130: 446-450.
21. Appel LJ,MooreTJ,Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Eng J of Med. 1997;336 (16):1117-1124.
22. Conlin PR, Chow D, Miller ER, et al. The effect of dietary patterns on blood pressure control in hypertensive patients: results from the Dietary Approaches to Stop Hypertension (DASH) trial. Am J Hypertens. 2000;13:949-955.
23. Stein M, Wark JD, Scherer SC. Falls relate to vitamin D and parathyroid hormone in an Australian nursing home and hosteU Am Geriatr Soc. 1999; 47:1195-1201.
24. Sato Y, lnose M, Higuchi I, Kondo I. Changes in the supporting muscles of the fractured hip in elderly women. Bone. 2002; 30:325-330.
25. Janssen HC, Samson MM,Verhaar HJ. Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr. 2002,75:611-615.
26. Geusens P,Vandevyver C,Vanhoof J,Cassiman JJ, Boonen S, Raus J. Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women. J Bone Miner Res. 1997;12:2082-2088.
27. Patten BM, Pages M. Severe neurological disease associated with hyperpararthyroidism. Ann Neural. 1984;15: 453-486.
28. Pfeifer M, Begerow B, Minne HW, et al. Vitamin D status, trunk muscle strength, body sway, falls, and fractures among 237 postmenopausal women with Osteoporosis. Exp CHn Endocrinol Diabetes. 2001 ;109:87-92.
29. Dhesi JK, Bearne LM, Moniz C, et al. Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. J Bone Miner Res. 2002;17:891 -897.
30. Dhesi JK,MonizC,CloseJC,JacksonSH,AllainTJ. A rationale for vitamin D prescribing in a falls clinic population. Age Ageing. 2002;31:267-271.
31. Russell RM. Vitamin requirements in old age. Age Nutrition. 1992;3:20-23.
Karen Friel, PT, MHS
Assistant Professor, New York Institute of Technology, Department of Physical Therapy
Address correspondence to: Karen Friel, PT, MHS, New York Institute of Technology, Department of Physical Therapy, Room 501, Northern Boulevard, PO Box 8000 Old Westbury, NY 11568-8000, Phone: 516-686-7651, Fax: 516-686-7699 (Email: Kfriel@nyit.edu).
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