Osteoporosis, calcium - NCBI - NIH

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de la vente des supplements calciques, car les femmes d'age moyen cherchent a ... and the College ofPhysical Education, University ofSaskatche- wan, Saskatoon .... difficult, however, because of the various tech- niques used to measureĀ ...

I Current Review

Osteoporosis, calcium and physical activity Alan D. Martin, PhD C. Stuart Houston, MD

Sales of calcium supplements have increased dramatically since 1983, as middle-aged women seek to prevent or treat bone loss due to osteoporosis. However, epidemiologic studies have failed to support the hypothesis that larger amounts of calcium are associated with increased bone density or a decreased incidence of fractures. The authors examine the evidence from controlled trials on the effects of calcium supplementation and physical activity on bone loss and find that weight-bearing activity, if undertaken early in life and on a regular basis, can increase the peak bone mass of early adulthood, delay the onset of bone loss and reduce the rate of loss. All of these factors will delay the onset of fractures. Carefully planned and supervised physical activity programs can also provide a safe, effective therapy for people who have osteoporosis.

Depuis 1983 on assiste a une montee en fl'eche de la vente des supplements calciques, car les femmes d'age moyen cherchent a prevenir ou a traiter une deperdition osseuse par osteoporose, malgre l'absence de preuves epidemiologiques qu'une plus forte ingestion de calcium puisse augmenter la densite osseuse ou abaisser. la frequence des fractures. On passe ici en revue les travaux comparatifs sur le rapport entre l'usage de tels supplements d'une part, et l'exercice physique d'autre part, et la deperdition osseuse. II appert que les activites non sedentaires entreprises tot dans la vie et poursuivies fidelement vont augmenter la masse osseuse From the Department of Medical Imaging, University Hospital, and the College of Physical Education, University of Saskatchewan, Saskatoon

Reprint requests to: Dr. Alan D. Martin, Department of Medical Imaging, University Hospital, Saskatoon, Sask. S7N OXO

chez l'adulte jeune, retarder le moment ou spinstallera la deperdition osseuse et en ralentir le rythme: trois facteurs susceptibles de repousser l'age du debut des fractures. Quant aux sujets deja atteints d'osteoporose, les programmes d'activite physique bien adaptes et bien surveilles peuvent leur offrir une thErapeutique sure et efficace.

I nterest in calcium intake is at an all-time high. Annual sales of calcium supplements in the United States were projected to reach $200 million by 1987, an increase of more than 300% from the 1983 figures.1 Intensive advertising campaigns by the pharmaceutical, dairy and health food industries have been supported by statements similar to that of the National Institutes of Health Consensus Development Conference on Osteoporosis: a daily calcium intake of 1000 to 1500 mg should be started in women "well before" menopause.2 There have been calls for an increased recommended dietary allowance: Heaney and Recker' found that 23% of estrogen-deprived women without osteoporosis did not absorb adequate amounts of calcium at a daily intake of 1500 mg and that 12% of such women did not absorb adequate amounts at a daily intake of 2500 mg. Nutritionists and dietitians have been among the most vocal opponents of those who suggest that people benefit from high doses of nutrients such as vitamin C, niacin and vitamin E. Why is there a different perspective on calcium? Osteoporosis is the most common skeletal disorder in North America. Figures from the United States indicate that 15 to 20 million adults are affected and that this involves 1.3 million fractures and an annual cost of $3.8 billion for treatment.24 The estimated 267 000 fractures of the femoral neck that occurred in 1980 resulted in costs of $1.3 billion for acute care alone5 and in average hospital stays of 21 days.6 The mortality rate 6 months after CMAJ, VOL. 136, MARCH 15, 1987


hip fractures has ranged from 5% to 15%;5 only 25% of the survivors fully recover, 50% need assistance in carrying out their daily activities and 25% are totally disabled.7'8 The incidence of fractures due to osteoporosis is increasing. Although the number of women over 65 years of age with such fractures rose by 30.8% in 1970-80, the number of hip fractures increased by 35.5% and the number of vertebral fractures by 40%.5 These unexplained increases in true incidence have also been observed in Britain.9 Osteoporosis is the result of progressive bone loss. The loss of trabecular bone begins in the third decade of life for both sexes,'0-15 but the loss of cortical bone usually begins a decade or so later.16 Although the age at onset and the rate vary,17 bone loss clearly occurs well before menopause and in both sexes. For women the loss increases greatly from the premenopausal rate of about 3% per decade to the annual postmenopausal rates of 3% to 10% for trabecular bone18 and 1% to 2% for cortical bone.19 This rapid, exponential loss of trabecular bone results in fractures of the distal radius and vertebrae, two skeletal sites having a high trabecular:cortical ratio,17 and has been termed type 1 (postmenopausal) osteoporosis.20 Fractures of the proximal femur, which has a higher content of cortical bone, usually occur after 60 years of age and reflect the shifting emphasis to cortical bone loss in the elderly: type 2 (senile) osteoporosis. The cumulative incidence rates of hip fractures are 33% in women and 17% in men who live to 90 years of age.21 Vertebral damage due to osteoporosis is more difficult to quantify than hip fractures since it may be asymptomatic; however, by 70 years of age 25% of women have a complete or partial vertebral fracture.18 Anterior wedge fractures lead to thoracic kyphosis ("dowager's hump") and, with other forms of compression fracture, are responsible for the progressive loss in height of some 4 cm per decade, a process that may continue until the rib cage settles on the iliac crest. The chronologic sequence of fractures is represented in Fig. 1. The irreversible nature of spinal deformities, the severe impact of hip fractures on lifestyle and the limited effectiveness of most therapies make prevention of osteoporosis of paramount importance. Three main factors affect bone mass: estrogen, diet and physical activity. The effectiveness of estrogen in preventing the rapid loss of bone in the 5- to 10-year period after menopause has been well documented by means of double-blind trials18 and will not be discussed here.

Vitamin D Although other nutrients, such as protein, phosphate and sodium, affect bones, most research has focused on vitamin D and calcium. Vitamin D, more properly regarded as a hormone,23 acts to increase the availability of calcium and phosphate by increasing the absorption of these minerals from the gastrointestinal tract and by liberating them through bone resorption.24 Calcitriol, the most important metabolite of vitamin D, acts on bone much like parathyroid hormone in that it inhibits bone collagen synthesis25 and increases bone resorption. The finding that serum calcitriol levels in patients with osteoporosis are similar to those of healthy age-matched subjects26-28 supports the conclusion that vitamin D should not be used in treating postmenopausal osteoporosis,22'28 where it has been shown either to have no effect29'30 or to increase the loss of cortical bone.31 Its effectiveness in treating senile osteoporosis has yet to be assessed.

Calcium In animals the well-established observation that calcium deficiency results in osteoporosis has led to the argument that calcium deficiency is an important factor in human osteoporosis.32 Much evidence from the measurement of bone mass, fracture rates and calcium balance is available to assess the validity of this argument. Analysis is difficult, however, because of the various techniques used to measure bone status: biopsy, radiogrammetry, radiographic densitometry, single- and dual-photon absorptiometry, neutron activation, Compton scattering and quantitative computed tomography.33 Such techniques may be applied at many different skeletal sites, including the calcaneus, various positions on the radius and ulna, the metacarpals, the femoral neck and shaft, the iliac crest and the vertebrae. Epidemiologic evidence does not support the

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Parfitt22 reviewed dietary risk factors for agerelated bone loss and stated that "bone mass normally depends less on nutrition than on age, sex, race and other features of genetic constitution, muscular activity and hormonal state". 588

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60 Age (yr)

Fig. 1 - Schematic model of trabecular and cortical bone loss with increasing age in women.

hypothesis that larger intakes of calcium are associated with increased bone density or a decreased incidence of fractures. The populations of many third-world countries have low calcium intakes but little osteoporosis,34-37 and in Western countries measurements of bone mass and calcium consumption are poorly related.38-41 Proponents of the calcium hypothesis frequently cite the study of Matkovic and associates,42 who found a significantly lower incidence of hip fractures in subjects taking large amounts of calcium than in those taking small amounts. However, age-related bone loss was greater in the first group, and they concluded the following: "The data suggest that nutrition (in particular the calcium intake) is an important determinant of bone mass in young adults but seems to have little effect on age-related bone loss in either males or females." If this is true, calcium supplementation in adults is ineffective in preventing bone loss or fractures due to osteoporosis. The effects on bone of different amounts of calcium taken during childhood are unclear. There is some evidence that increased levels of dietary calcium in children have been responsible for the secular trend to increased stature in Britain and Japan43-45 and that milk consumption during childhood may lead to increased bone density in middle age.34 Cross-sectional studies are, however, subject to errors that mainly arise in assessing diet, particularly if the subjects are recalling eating habits of several decades ago. In addition, present eating habits, even if accurately assessed, may have little bearing on the current skeletal status. Prospective trials overcome some of these difficulties and have the potential to investigate

causality. The results of controlled studies that examined the effects of calcium supplementation on bone in healthy postmenopausal women are summarized in Table 1.46-52 One of the three studies before 1980 used the now somewhat obsolete method of radiographic densitometry and showed increased phalanx density;46 the other two used single-photon absorptiometry and radiogrammetry and showed mixed results.47'48 Smith and colleagues49 were the only ones to show a significant effect of calcium supplementation on the bone mineral content of the distal radius, a common fracture site in osteoporosis. They were also the only ones to observe elderly subjects (mean age 82 years). Nilas and collaborators50 divided their subjects into three groups on the basis of their usual daily calcium intake: less than 550 mg, between 550 mg and 1150 mg, and more than 1150 mg. All took a 500-mg calcium supplement daily for 2 years, and the bone mineral content of the distal forearm was measured by single-photon absorptiometry every 3 months. The mean percentage of bone loss did not differ significantly between the groups (3.8%, 3.2% and 4.0% respectively). There was even no difference in bone loss between the 14 women with daily calcium intakes greater than 1800 mg and the 14 with the lowest intake (3.9% and 4.1% respectively). The number of measurements and the high precision (each measurement was the mean of 12 scans) strengthened the findings of this study. Ettinger and coworkers52 combined quantitative computed tomography of the lumbar spine, single-photon absorptiometry of the distal radius and metacarpal radiogrammetry in a recent 2-year

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trial to assess the effect of a daily calcium supplement of 1000 mg on bone but found no differences between the experimental and control groups. From this evidence the case for calcium supplementation in healthy postmenopausal women has clearly not been proved. However, the most likely subjects to respond would be those who already have osteoporosis. This has been investigated by five groups,3153 56 and their results are summarized in Table II. Only Riggs and associates56 showed a statistically significant effect of calcium supplementation on bone status, demonstrating a decreased incidence of vertebral fractures in the group taking calcium supplements. The conclusion must be that calcium supplementation does not significantly decrease the incidence of bone loss in postmenopausal women with or without osteoporosis. No trials have been carried out on men, young women or children, although preliminary evidence suggests a possible effect among children.42

Physical activity Although the impact of environmental factors on the mass and distribution of adipose tissue and muscle is well accepted, the dynamic nature of bone is not. Bone tissue reorganizes when the applied mechanical forces change, a principle Wolff recognized almost 100 years ago.57 Results of studies in animals have clearly shown that bone architecture, rather than the quality of the bone tissue, changes in response to changing loads.58 The extreme situation of disuse results in a rapid reduction of bone mass. Astronauts subjected to a gravity-free environment lose bone at a monthly rate of about 4% for trabecular bone and 1% for cortical bone.59 Similar rates have been reported with the use of casts after sports injuries60 and with immobility because of denerva-


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tion,61 paraplegia, poliomyelitis62 and bed rest.59 The phenomenon is also regularly observed qualitatively by clinical radiologists.63 Normal bone mass usually retums when gravitational forces are reimposed; however, this process is considerably slower than the loss of bone mass and may not be complete in some people.59 Equally convincing is the evidence of greater bone mass and strength resulting from high activity levels in animals. Regimens of weight-bearing activity have been shown to increase bone mass in mice, rats, rabbits, turkeys, dogs, sheep and pigs.5864-72 In humans, cross-sectional studies have shown that those accustomed to higher levels of physical activity tend to have greater bone mass. Athletes have been found to have higher bone density than nonathletes,73 and experienced runners have been found to have greater bone mineral content than control subjects.74-76 Regular strenuous exercise has been associated with higher bone mineral content; this effect has been found in subjects 25 years of age who were active as adolescents.77 The low bone density usually associated with amenorrhea due to anorexia nervosa is less evident in those who are physically active.78 The main difficulty in cross-sectional studies is in quantifying levels of physical activity. Several large-scale studies have failed to find an association between bone density and self-reported activity levels.79-81 Subjective perception of effort and energy output during normal daily activities vary considerably, and at best questionnaires do not accurately assess activity.82 Prospective studies address the issue of physical activity and bone density directly. We found six such studies in the literature (Table III).49,83-87 Photon absorptiometry was used in all the studies to assess bone changes. In five studies significant positive effects of a regular program of physical activity were observed. Bone measurements of the distal radius did not differ; however, two studies

showed a significant increase in the bone mineral content of weight-bearing sites (lumbar vertebrae and the calcaneus) in the active groups.84'87 Conclusions Increasing the dietary intake of a mineral does not in itself ensure metabolic use of that mineral. Uptake by a specific tissue depends largely on the needs of the tissue cells. Bone is no exception: it will absorb or eliminate calcium to maintain the mineral:osteoid ratio and absolute amount of bone needed to meet changing mechanical stresses. Lanyon88 hypothesized that any functional level of bone mass is attained and maintained through the balance of a mechanically engendered osteogenic stimulus and a net hormonal drive toward resorption. Therefore, one can conclude the following: functional activity must continue for bone mass to be maintained; increased activity results in increased bone mass; and reduced activity induces hormone-mediated bone loss. Bone loss due to osteoporosis has been considered by some to be irreversible.89'90 This view is well-founded if only biochemical factors are considered. Heaney91 concluded that "neither calcium nor estrogen will reverse the bone loss once it has occurred". From the data reviewed here the rate of bone loss has not even been decreased by calcium supplementation. However, if mechanical factors are considered, as they must be, bone formation can apparently be promoted in adults with or without osteoporosis. An important question remains: How does the type and intensity of physical activity affect bone formation? This question has not been fully answered, although some facts are clear. The activity must be weight-bearing; for example, the bone density of swimmers, unlike other athletes, does not differ significantly from that of nonathletes.73 The stresses induced in bone by muscle tension seem to have a more local effect, such as changing trabecular density within tuberosities, rather than an overall effect, as is induced by compressive loading. The importance of weight-bearing can







also be seen in the tendency of trabeculae to be arranged along the lines of principal tension and compression,92 such patterns being most evident in the femoral neck.63 Dynamic loading has recently been found necessary to stimulate bone modelling. It is the rate of change of strain within bone, rather than the magnitude of strain, that dictates the osteogenic drive.92 In addition, relatively few strain cycles are needed daily for maximum effect: in roosters 1800 strain cycles daily had no greater effect on bone mass or architecture of the ulna than 36 cycles daily.93 This study also demonstrated that bone mass is greatly influenced by the diversity of its loading pattern as well as by the strain rate. These findings suggest general aspects of a bone-conserving or bone-promoting exercise regimen. Such activities should include a wide variety of loading situations and should be vigorous enough to produce high strain rates.92 For those who already have osteoporosis or are at risk, caution must be observed, particularly in the early stages of a new exercise program; skill and sensitivity is required in the design and execution of such a program. Regular physical activity as therapy is less attractive than chemical intervention, but the advantages go far beyond the maintenance of skeletal integrity.94 The magnitude of the problem and the intractable nature of osteoporosis reinforce the importance of prevention. Regular physical activity, started early in childhood, can increase the peak bone mass of early adulthood, delay the onset of bone loss and reduce the rate of loss; all of these factors will help to delay the onset of fractures. In addition, regular weight-bearing activity, if done carefully, currently provides a safe, effective form of therapy for those at risk for osteoporotic fracture.

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tation. Acta Orthop Scand 1978; 49: 143-146 56. Riggs BL, Seeman E, Hodgson SF et al: Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis. Comparison with conventional therapy. NEnglJMed 1982; 306: 446-450 57. Wolff J: The Law of Bone Transformation, Hirschwald, Berlin, 1892 58. Woo SL, Kuei S, Amiel D et al: The effect of prolonged physical training on the properties of long bone: a study of Wolff's law. J Bone Joint Surg [Am] 1981; 63: 780-786 59. Mazess RB, Whedon GD: Immobilization and bone. Calcif Tissue Int 1983; 35: 265-267 60. Andersson SM, Nilsson BE: Changes in bone mineral content following ligamentous knee injuries. Med Sci Sport Exerc 1979; 11: 351-353 61. Brighton CT, Katz MJ, Goll SR et al: Prevention and treatment of sciatic denervation disuse osteoporosis in the rat tibia. Bone 1985; 6: 87-97 62. Abramson AS, Delagi EF: Influence of weight-bearing and muscle contraction on disuse osteoporosis. Arch Phys Med Rehabil 1961; 42: 147-151 63. Houston CS: The radiologist's opportunity to teach bone dynamics. J Can Assoc Radiol 1978; 29: 232-238 64. Kiiskinen A, Heikkinen E: Physical training and connective tissues in young mice: biochemistry of long bones. J Appi Physiol 1978; 44: 50-54 65. Bell RR, Tzeng DY, Draper HH: Long-term effects of calcium, phosphorus and forced exercise on the bones of mature mice. J Nutr 1980; 110: 1161-1167 66. Saville PD, Whyte MP: Muscle and bone hypertrophy: positive effect of running exercise in the rat. Clin Orthop 1969; 65: 81-88 67. Burr DB, Martin RB, Martin PA: Lower extremity loads stimulate bone formation in the vertebral column: implications for osteoporosis. Spine 1983; 8: 681-686 68. Rubin CT, Lanyon LE: Regulation of bone mass by mechanical strain magnitude. Calcif Tissue Int 1985; 37: 411417 69. Martin RK, Albright JP, Clarke WR et al: Load-carrying effects on the adult beagle tibia. Med Sci Sports Exerc 1981; 13: 343-349 70. Chamay A, Tschantz P: Mechanical influences in bone remodelling. Experimental research on Wolff's law. J Biomech 1972; 5: 173-180 71. Lanyon LE, Rubin CT: Regulation of bone mass in response to physical activity. In Dixon A, Russell RG, Stamp TCB (eds): Osteoporosis: a Multidisciplinary Problem (R Soc Med Int Congr Symp ser), Acad Pr, London, 1983: 51-61 72. Goodship AE, Lanyon LE, McFie H: Functional adaptation of bone to increased stress. J Bone Joint Surg [Am] 1979; 61: 539-546 73. Nilsson BE, Westlin NE: Bone density in athletes. Clin Orthop 1971; 77: 179-182 74. Dalen N, Olssen KE: Bone mineral content and physical activity. Acta Orthop Scand 1974; 45: 170-174 75. Brewer V, Meyer BM, Keele MS et al: Role of exercise in

prevention of involutional bone loss. Med Sci Sports Exerc 1983; 15: 445-449 76. Lane NE, Bloch DA, Jones HH et al: Long distance running, bone density and osteoarthritis. JAMA 1986; 255: 11471151 77. Talmage RV, Anderson JB: Bone density loss in women: effects of childhood activity, exercise, calcium intake and estrogen therapy [abstr]. Calcif Tissue Int 1984; 36: S52 78. Rigotti NA, Nussbaum SR, Hertzog DB et al: Osteoporosis in women with anorexia nervosa. N Engi J Med 1984; 311: 1601-1606 79. Montoye HJ, McCabe JF, Metzner HL et al: Physical activity and bone density. Hum Biol 1976; 48: 599-610 80. Johnell 0, Nilsson BE: Lifestyle and bone mineral mass in perimenopausal women. Calcif Tissue Int 1984; 36: 354356 81. Borkan GA, Norris AH: Biological age in adulthood: comparison of active and inactive males. Hum Biol 1980; 52: 787-802 82. Washburn RA, Montoye HJ: The assessment of physical activity by questionnaire. Am J Epidemiol 1986; 123: 563576 83. Aloia JF, Cohn SH, Ostuni JA et al: Prevention of involutional bone loss by exercise. Ann Intern Med 1978; 89: 356-358 84. Krolner B, Toft B, Nielsen SP et al: Physical exercise as prophylaxis against involutional vertebral bone loss: a controlled trial. Clin Sci 1983; 64: 541-546 85. Smith EL, Smith PE, Ensign CJ et al: Bone involution decrease in exercising middle-aged women. Calcif Tissue Int 1984; 36 (suppl): S129-S138 86. White MK, Martin RB, Yeater RA et al: The effects of exercise on the bones of postmenopausal women. Int Orthop 1984; 7: 209-214 87. Williams JA, Wagner J, Wasnich R et al: The effect of long-distance running upon appendicular bone mineral content. Med Sci Sports Exerc 1984; 16: 223-227 88. Lanyon LE: Osteoporosis and mechanically related bone remodeling. In Menczel J, Robin GC, Makin M et al (eds): Osteoporosis, Wiley, New York, 1982: 148-156 89. Rose GA: The irreversibility of osteoporosis. In Barzel US (ed): Osteoporosis, Grune, New York, 1970: 123-132 90. Parfitt AM: The integration of skeletal and mineral homeostasis. In DeLuca HF, Frost HM, Jee WS et al (eds): Osteoporosis: Recent Advances in Pathogenesis and Treatment, Univ Park, Baltimore, 1981: 115-121 91. Heaney RP: Paradox of irreversibility of age-related bone loss. In Menczel J, Robin GC, Makin M et al (eds): Osteoporosis, Wiley, New York, 1982: 15-20 92. Lanyon LE, Rubin CT, O'Connor JE et al: The stimulus for mechanically adaptive bone remodeling. Ibid: 135-147 93. Rubin CT, Lanyon LE: Bone remodeling in response to applied dynamic loads. Orthop Trans 1981; 5: 2-37 94. Paffenbarger RS, Hyde RT, Wing AL et al: Physical activity; all-cause mortality and longevity of college alumni. N Engi JMed 1986; 314: 605-613

The advantage of medicine The advantage that the practice of medicine has over surgery is, that if you do not know what the matter is, you can call it occult, and get off with credit, but as surgery is demonstrable, they hold you to the proof.

Nicholas de Belleville (1753-1831)

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