Abstract
Osteoporosis is a serious health problem that diminishes quality of life and levies a financial burden on those who fear and experience bone fractures. Physical activity as a way to prevent osteoporosis is based on evidence that it can regulate bone maintenance and stimulate bone formation including the accumulation of mineral, in addition to strengthening muscles, improving balance, and thus reducing the overall risk of falls and fractures. Currently, our understanding of how to use exercise effectively in the prevention of osteoporosis is incomplete. It is uncertain whether exercise will help accumulate more overall peak bone mass during childhood, adolescence and young adulthood. Also, the consistent effectiveness of exercise to increase bone mass, or at least arrest the loss of bone mass after menopause, is also in question. Within this framework, section 1 introduces mechanical characteristics of bones to assist the reader in understanding their responses to physical activity.
Section 2 reviews hormonal, nutritional and mechanical factors necessary for the growth of bones in length, width and mineral content that produce peak bone mass in the course of childhood and adolescence using a large sample of healthy Caucasian girls and female adolescents for reference. Effectiveness of exercise is evaluated throughout using absolute changes in bone with the underlying assumption that useful exercise should produce changes that approximate or exceed the absolute magnitude of bone parameters in a healthy reference population. Physical activity increases growth in width and mineral content of bones in girls and adolescent females, particularly when it is initiated before puberty, carried out in volumes and at intensities seen in athletes, and accompanied by adequate caloric and calcium intakes. Similar increases are seen in young women following the termination of statural growth in response to athletic training, but not to more limited levels of physical activity characteristic of longitudinal training studies. After 9–12 months of regular exercise, young adult women often show very small benefits to bone health, possibly because of large subject attrition rates, inadequate exercise intensity, duration or frequency, or because at this stage of life accumulation of bone mass may be at its natural peak. The important influence of hormones as well as dietary and specific nutrient abundance on bone growth and health are emphasised, and premature bone loss associated with dietary restriction and estradiol withdrawal in exercise-induced amenorrhoea is described.
In section 3, the same assessment is applied to the effects of physical activity in postmenopausal women. Studies of postmenopausal women are presented from the perspective of limitations of the capacity of the skeleton to adapt to mechanical stress of exercise due to altered hormonal status and inadequate intake of specific nutrients. After menopause, effectiveness of exercise to increase bone mineral depends heavily on adequate availability of dietary calcium. Relatively infrequent evidence that physical activity prevents bone loss or increases bone mineral after menopause may be a consequence of inadequate calcium availability or low intensity of exercise in training studies. Several studies with postmenopausal women show modest increases in bone mineral toward the norm seen in a healthy population in response to high-intensity training. Physical activities continue to stimulate increases in bone diameter throughout the lifespan. These exercise-stimulated increases in bone diameter diminish the risk of fractures by mechanically counteracting the thinning of bones and increases in bone porosity.
Seven principles of bone adaptation to mechanical stress are reviewed in section 4 to suggest how exercise by human subjects could be made more effective. They posit that exercise should: (i) be dynamic, not static; (ii) exceed a threshold intensity; (iii) exceed a threshold strain frequency; (iv) be relatively brief but intermittent; (v) impose an unusual loading pattern on the bones; (vi) be supported by unlimited nutrient energy; and (vii) include adequate calcium and cholecalciferol (vitamin D3) availability.
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References
World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: report of a WHO Study Group. Geneva: World Health Organization, 1994
Bone Health and Osteoporosis: a report of the Surgeon General. Rockville (MD): US Department of Health and Human Services, Office of the Surgeon General, 2004
Ray NF, Chan JK, Thamer M, et al. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res 2003; 12: 24–35
Newton-John HF, Morgan DB. Osteoporosis: disease or senescence? Lancet 1968; I: 232–3
Albright F, Smith PH, Richardson AM. Postmenopausal osteoporosis. JAMA 1941; 116: 2465–74
Riis BJ, Hansen MA, Jensen AM, et al. Low bone mass and fast bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study. Bone 1996; 19: 9–12
Genant HK, Grampp S, Gluer CC, et al. Universal standardization for dual x-ray absorptiometry: patient and phantom cross-calibration results. J Bone Miner Res 1994; 9: 1503–14
Kelley GA. Aerobic exercise and bone density at the hip in postmenopausal women: a meta-analysis. Prev Med 1998; 27: 798–807
Snow CM, Shaw JM, Matkin CC. Physical activity and risk for osteoporosis. In: Marcus R, Feldman D, Kelsey J, editors. Osteoporosis. New York: Academic Press, 1996: 511–28
Snow-Harter C, Marcus R. Exercise, bone mineral density, and osteoporosis. Exerc Sport Sci Rev 1992; 7: 1291–6
Wallace BA, Cumming RG. Systematic review of randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women. Calcif Tissue Int 2000; 67: 10–8
Ham AW. Histology. 7th ed. Philadelphia (PA): Lippincott, 1974: 417
Mosekilde L. Age-related changes in vertebral trabecular bone architecture -assessed by a new method. Bone 1988; 9: 247–50
Wolff J. Das Gesetz der Transformation der Knochen. Berlin: Hirschwald, 1892
Wolff J. The law of bone remodelling. New York (NY): Springer, 1986
Wahner HW, Dunn WL, Riggs BL. Assessment of bone mineral, part 1. J Nucl Med 1984; 25: 1134–41
Jee WSS. Integrated bone tissue physiology: anatomy and physiology. In: Cowan SC, editor. Bone mechanics handbook. 2nd ed. Boca Raton (FL): CRC Press, 2001: 1–68
Nottestadt SY, Baumel JJ, Kimmel DB, et al. The proportion of trabecular bone in human vertebrae. J Bone Miner Res 1987; 2: 221–2
Schlenker RA, Von Seggen WW. The distribution of cortical and trabecular bone mass along the lengths of the radius and ulna and the implication for in vivo bone mass measurements. Calcif Tissue Int 1994; 308: 1543–4
Riggs BL, Wahner HW, Seeman E, et al. Changes in bone mineral density of the proximal femur and spine with aging. J Clin Invest 1982; 70: 716–23
Abramson AS. Bone disturbances in injuries to the spinal chord and cauda equina (paraplegia): their prevention by ambulation. J Bone Joint Surg 1948; 30A: 982–7
Donaldson CL, Hulley SB, Vogel JM, et al. Effect of prolonged bed rest on bone mineral. Metabolism 1970; 19: 1071–84
Krolner B, Toft B. Vertebral bone loss: an unheeded side effect of therapeutic bed rest. Clin Sci 1983; 64: 537–40
Mazess RB, Whedon GD. Immobilization and bone. Calcif Tissue Int 1983; 35: 265–7
Prince RL, Price RI, Ho S. Forearm bone loss in hemiplegia: a model for the study of immobilization osteoporosis. J Bone Miner Res 1988; 3: 305–10
Rambaut PC, Dietlein LF, Vogel JM, et al. Comparative study of two direct methods of bone mineral measurement. Aerosp Med 1972; 43: 646–50
Stewart AF, Adler M, Byers CM, et al. Calcium homeostasis in immobilization: an example of resorptive hypercalciuria. N Engl J Med 1982; 306: 1136–40
Whedon GD. Disuse osteoporosis: physiological aspects. Calcif Tissue Int 1984; 36 Suppl. 1: S146–50
Collet P, Uebelhart D, Vico L, et al. Effects of 1- and 6-month spaceflight on bone mass and biochemistry in two humans. Bone 1997; 20: 547–51
LeBlanc A, Schneider V, Shackelford L, et al. Bone mineral and lean tissue loss after long duration spaceflight. J Bone Miner Res 1976; 11 Suppl. 1: 567
Mack PB, LaChance PA, Vose GP, et al. Bone demineralization of foot and hand of Gemini-Titan IV, V, and VII astronauts during orbital flight. Am J Roentgenol Radium Ther Nucl Med 1967; 100: 503–11
Vogel JM, Whittle MW. Bone mineral changes: the second manned Skylab mission. Aviat Space Environ Med 1976; 47: 396–400
Bassett CA, Becker RO. Generation of electrical potentials by bone in response to mechanical stress. Science 1962; 137: 1063–4
Burger EH, Klein-Nilend J. Mechanotransduction in bone: role of the lacuno-canalicular network. FASEB J 1999; 13 Suppl.: S101–12
Smit TH, Burger EH, Huyghe JM. A case for strain-induced fluid flow as a regulator of BMU-coupling and osteonal alignment. J Bone Miner Res 2002; 17: 2021–9
Recker RR, editor. Bone histomorphometry: techniques and interpretation. Boca Raton (FL): CRC Press, 1983
Marcus R. Normal and abnormal bone remodeling in man. Adv Intern Med 1987; 38: 129–41
Genant HK, Lang TF, Engelke K, et al. Advances in the noninvasive assessment of bone density, quality, and structure. Calcif Tissue Int 1996; 59 Suppl. 1: S10–5
Health and Public Policy Committee, American College of Physicians. Radiologic methods to evaluate bone mineral content. Ann Intern Med 1984; 100: 908–11
Dalsky GP, Stocke KS, Ehsani AA, et al. Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women. Ann Intern Med 1988; 108: 824–8
Grove KA, Londeree BR. Bone density in postmenopausal women: high impact vs low impact exercise. Med Sci Sports Exerc 1992; 24: 1190–4
Nelson ME, Fisher EC, Dilmanian A, et al. A 1-y walking program and increased dietary calcium in postmenopausal women: effects on bone. Am J Clin Nutr 1991; 53: 1304–11
Pruitt LA, Jackson RD, Bartels RL, et al. Weight-training effects on bone mineral density in early postmenopausal women. J Bone Miner Res 1992; 7: 179–85
Sowers M, Galuska DA. Epidemiology of bone mass in premenopausal women. Epidemiol Rev 1993; 15: 374–98
Haapasalo H, Sievanen H, Kannus P, et al. Dimensions and estimated mechanical characteristics of the humerus after long-term tennis loading. J Bone Miner Res 1996; 11: 864–72
Sievanen H, Kannus P, Nieminen V, et al. Estimation of various mechanical characteristics of human bones using dual energy x-ray absorptiometry. Bone 1996; 18: 517–26
Genant HK, Gluer CC, Lotz JC. Gender differences in bone density, skeletal geometry, and fracture biomechanics. Radiology 1994; 190: 636–40
Carter DR, van der Meulen MCH, Beaupré GS. Skeletal development: Mechanical consequences of growth, aging, and disease. In: Marcus R, Feldman D, Kelsey J, editors. Osteoporosis. New York (NY): Academic Press, 1996: 333–50
Cann CE. Low-dose CT scanning for qualitative spinal mineral analysis. Radiology 1981; 140: 813–5
Sievanen H, Koskue V, Rauhio A, et al. Peripheral quantitative computed tomography in human long bones: evaluation of in vitro and in vivo precision. J Bone Miner Res 1998; 13: 871–82
Harrison JE, McNeill KG, Hitchman AJ, et al. Bone mineral measurement of central skeleton by neutron activation analysis for routine investigation of osteopenia. Invest Radiol 1979; 14: 27–34
Hazan G, Leichter I, Loewinger E, et al. Early detection of osteoporosis by Compton gamma ray spectroscopy. Phys Med Biol 1977; 22: 1073–84
Rhodes EC, Martin AD, Taunton JE, et al. Effects of one-year of resistance training on the relations between muscular strength and bone density in elderly women. Br J Sports Med 2000; 34: 18–22
Ayalon J, Simkin A, Leichter I, et al. Dynamic bone loading exercises for postmenopausal women: effect on the density of the distal radius. Arch Phys Med Rehabil 1987; 68: 280–3
Gerdhem P, Akesson K, Obrant KJ. Effect of previous and present physical activity on bone mass in elderly women. Osteoporos Int 2003; 14: 203–12
Ringsberg KAM, Gardsell P, Johnell O, et al. The impact of long-term moderate physical activity on functional performance, bone mineral density and fracture incidence in elderly women. Gerontology 2001; 47: 15–20
Ulrich CM, Georgious CC, Snow-Harter CM, et al. Bone mineral density in mother-daughter pairs: relations to lifetime exercise, lifetime milk consumption, and calcium supplements. Am J Clin Nutr 1996; 63: 72–9
Gleeson PB, Protas EJ, LeBlanc AD, et al. Effects of weight lifting on bone mineral density in premenopausal women. J Bone Miner Res 1990; 5: 153–8
Bassey EJ, Rothwell MC, Littlewood JJ, et al. Pre- and postmenopausal women have different bone mineral density responses to the same high-impact exercise. J Bone Miner Res 1998; 13: 1805–13
Hawkins SA, Schroeder ET, Wiswell RA, et al. Eccentric muscle action increases site-specific osteogenic response. Med Sci Sports Exerc 1999; 31: 1287–92
Lohman T, Going S, Pamenter R, et al. Effects of resistance training on regional and total bone mineral density in premenopausal women: a randomized prospective study. J Bone Miner Res 1995; 10: 1015–24
Snow-Harter C, Bouxsein CM, Lewis BT, et al. Muscle strength as a predictor of bone mineral density in young women. J Bone Miner Res 1990; 5: 589–95
Vuori I, Heinonen A, Sievanen H, et al. Effects of unilateral strength training and detraining on bone mineral density and content in young women: a study of mechanical loading and deloading on human bones. Calcif Tissue Int 1994; 55: 59–67
Chow R, Harrison JE, Notarius C. Effect of two randomized exercise programmes on bone mass of healthy postmenopausal women. BMJ 1987; 295: 1441–4
Heinonen A, Oja P, Sievanen H, et al. Effect of two training regimens on bone mineral density in healthy perimenopausal women: a randomized controlled trial. J Bone Miner Res 1998; 13: 483–9
Kemmler W, Engelke K, Weineck J, et al. The Erlangen fitness osteoporosis prevention study: a controlled exercise trial in early postmenopausal women with low bone density-First year results. Arch Phys Med Rehabil 2003; 84: 673–82
Kerr D, Ackland T, Maslen B, et al. Resistance training over 2 years increases bone mass in calcium-replete postmenopausal women. J Bone Miner Res 2001; 16: 175–81
Kerr D, Morton A, Dick I, et al. Exercise effects on the bone mass in postmenopausal women are site-specific and load-dependent. J Bone Miner Res 1996; 11: 218–25
Kohrt WM, Ehsani AA, Birge Jr SJ. Effects of exercise involving predominantly either joint-reaction ot ground-reaction forces on bone mineral density in older women. J Bone Miner Res 1997; 12: 1253–61
Mandalozzo GF, Snow CM. High intensity resistance training: effects on bone in older men and women. Calcif Tissue Int 2000; 66: 399–404
Nelson ME, Fiatarone MA, Morganti CM, et al. Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures: a randomized controlled trial. JAMA 1994; 272: 1909–14
Smith EL, Gilligan C, McAdam M, et al. Deterring bone loss by exercise intervention in premenopausal and postmenopausal women. Calcif Tissue Int 1989; 44: 312–21
Currey JD. Role of collagen and other organics in the mechanical properties of bone. Osteoporos Int 2003; 14 Suppl. 5: S29–36
Gardsell P, Johnell O, Nilsson BE. Predicting fractures in women by using forearm bone densitometry. Calcif Tissue Int 1989; 44: 235–42
Karlsson MK, Duan Y, Ahlborg H, et al. Age, gender, and fragility fractures are associated with differences in quantitative ultrasound independent of bone mineral density. Bone 2001; 28: 118–22
Seeman E. Periosteal bone formation: a neglected determinant of bone strength. N Engl J Med 2003; 349: 320–3
Hayes WC. Biomechanics of cortical and trabecular bone: implications for assessment of fracture risk. In: Mow WC, Hayes WC, editors. Basic orthopedic biomechanics. New York (NY): Raven Press, 1991: 93–142
van der Meulen MC, Beaupre GS, Carter DR. Mechanobiologic influences in long bone cross-sectional growth. Bone 1993; 14: 635–42
Parfitt AM. Age-related structural changes in trabecular and cortical bone: cellular mechanisms and biomechanical consequences. Calcif Tissue Int 1984; 36: 123–8
Currey JD. How well are bones designed to resist fracture? J Bone Miner Res 2003; 18: 591–8
Bell RH, Hawkins RJ. Stress fracture of the distal ulna. Clin Orthop 1986; 209: 169–71
Murakami Y. Stress fracture of the metacarpal in an adolescent tennis player. Am J Sports Med 1988; 16: 419–20
Rettig AC, Beltz HF. Stress fracture of the humerus in an adolescent tennis tournament player. Am J Sports Med 1985; 13: 55–8
Ammann P, Rizzoli R. Bone strength and its determinants. Osteoporos Int 2003; 14 Suppl. 3: S13–8
Ammann P, Rizzoli R, Meyer JM, et al. Bone density and shape as determinants of bone strength in IGF-I and/or pamidronate-treated ovariectomized rats. Osteoporos Int 1996; 6: 219–27
Turner CH, Burr DB. Basic biomechanical measurements of bone: a tutorial. Bone 1993; 14: 595–608
Riggs BL, Hodson SF, O’Fallon WM, et al. Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med 1990; 322: 802–9
Van Staa TP, Leufkens HGM, Abenhaim L, et al. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000; 15: 993–1000
Rodino MA, Shane E. Osteoporosis after organ transplant. Am J Med 1998; 104: 459–69
Schwartz AV, Sellmeyer DE, Ensrud KE, et al. Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 2001; 86: 32–8
Avioli LV. Significance of osteoporosis: a growing international health problem. Calcif Tissue Int 1991; 49S: S5–7
Evans WJ, Campbell W. Sarcopenia and age-related changes in body composition and functional capacity. J Nutr 1993; 123: 465–8
Cummings ST, Nevitt MC. Falls. N Engl J Med 1994; 331: 872–3
Nevitt MC, Cummings ST, Kidd S, et al. Risk factors for recurrent nonsycopal falls: a prospective study. JAMA 1989; 261: 2663–8
Tinetti ME, Baker DI, McAvay G, et al. A multifactorial intervention to reduce the risk of falling among elderly people living in the community. N Engl J Med 1994; 331: 821–7
Tinetti ME, Liu WL, Claus EB. Predictors and prognosis of inability to get up after falls among elderly persons. JAMA 1993; 269: 65–70
Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988; 319: 1701–7
Whipple RH, Wolfson LI, Amerman PM. The relationship of knee and ankle weakness to falls in nursing home residents: an isokinetic study. J Am Geriatr Soc 1987; 35: 13–20
Hui SL, Slemenda CW, Johnson Jr CC. Baseline measurement of bone mass predicts fracture in white women. Ann Intern Med 1989; 111: 355–61
Huopio J, Kroger H, Honkanen R, et al. Risk factors for perimenopausal fractures: a prospective study. Osteoporos Int 2000; 11: 219–27
Kanis JA, Delmas P, Burckhardt P, et al. Guidelines for diagnosis and management of osteoporosis. The European Foundation for Osteoporosis and Bone Disease. Osteoporos Int 1997; 7: 390–406
Kanis JA, Gluer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 2000; 11: 192–202
Kroger H, Huopio J, Honkanen R, et al. Prediction of fracture risk using axial bone mineral density in perimenopausal population: a prospective study. J Bone Miner Res 1995; 10: 302–6
Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone density predict occurrence of osteoporotic fractures. BMJ 1996; 312: 1254–9
Melton III LJ LJ, Atkinson EJ, O’Fallon WM, et al. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res 1993; 8: 1227–33
Broe KE, Hannan MT, Kiely DK, et al. Predicting fractures using bone mineral density: prospective study of long-term care residents. Osteoporos Int 2000; 11: 765–71
Duppe H, Gardsell P, Nilsson B, et al. A single bone density measurement can predict fractures over 25 years. Calcif Tissue Int 1997; 60: 171–4
Faulkner KG, Cummings SR, Black D, et al. Simple measurement of femoral geometry predicts hip fracture: the study of osteoporotic fractures. J Bone Miner Res 1993; 8: 1211–7
Faulkner KG. Bone matters: are density increases necessary to reduce fracture risk? J Bone Miner Res 2000; 15: 183–7
Cummings SR, Black DM, Nevitt MC, et al. Bone density at various sites for prediction of hip fractures. Lancet 1993; 421: 72–5
Duan Y, Parfitt A, Seeman E. Vertebral bone mass, size and volumetric density in women with spinal fractures. J Bone Miner Res 1999; 14: 1796–802
Seeman E, Duan Y, Fong C, et al. Fracture site-specific deficits in bone size and volumetric density in women with spinal fractures. J Bone Miner Res 2001; 16: 120–7
Evans RA, Marel GM, Lancaster EK, et al. Bone mass is low in relatives of osteoporotic patients. Ann Intern Med 1988; 109: 870–3
Seeman E, Hopper JL, Bach LA, et al. Reduced bone mass in daughters of women with osteoporosis. N Engl J Med 1989; 320: 554–8
Ahlborg HG, Johnell O, Turner CH, et al. Bone loss and bone size after menopause. N Engl J Med 2003; 349: 327–34
Cooper C, Eriksson JG, Forsen T, et al. Maternal height, childhood growth and risk of hip fracture in later life: a longitudinal study. Osteoporos Int 2000; 12: 623–9
Chan HH, Lau EM, Woo J, et al. Dietary calcium intake, physical activity and the risk of vertebral fracture in Chinese. Osteoporos Int 1997; 6: 228–32
Gregg EW, Cauley JA, Seeley DG, et al. Physical activity and osteoporotic fracture risk in older women. Ann Intern Med 1998; 129: 81–8
Lord SR, Ward JA, Williams P, et al. The effects of community exercise program on fracture risk factors in older women. Osteoporos Int 1996; 6: 361–7
Province MA, Hadley EC, Hornbrook MC, et al. The effects of exercise on falls in elderly patients. JAMA 1995; 273: 1341–7
Barnes GL, Kostenuik PJ, Gerstenfeld LC, et al. Growth factor regulation of fracture repair. J Bone Miner Res 1999; 14: 1805–15
Lushkey KL. Growth and development. In: Griffin JE, Ojeda SR, editors. Textbook of endocrine physiology. 1st ed. New York (NY): Oxford University Press, 1988: 209
Marshall WA, Tanner JM. Puberty. In: Falkner F, Tanner JM, editors. Human growth: a comprehensive treatise. New York (NY): Plenum Press, 1986: 171–209
Boyar RM, Katz J, Finkelstein JW, et al. Anorexia nervosa: Immaturity of the 24-hour luteinizing hormone secretory pattern. N Engl J Med 1974; 291: 861–5
Freedman DS, Khan LK, Serdula MK, et al. The relation of menarcheal age to obesity in childhood and adulthood: the Bogalusa heart study. BMC Pediatr 2003; 3: 3
Shalitin S, Phillip M. Role of obesity and leptin in the pubertal process and pubertal growth: a review. Int J Obes Relat Metab Disord 2003; 27: 869–74
Mauras N, Blizzard RM, Link K, et al. Augmentation of growth hormone secretion during puberty: evidence for a pulse amplitude-modulated phenomenon. J Clin Endocrinol Metab 1987; 64: 596–601
Brook CG, Hindmarsh PC. The somatotropic axis in puberty. Endocrinol Metab Clin North Am 1992; 21: 767–82
Zachman M. Interrelations between growth hormone and sex hormones: physiological and therapeutic consequences. Horm Res 1992; 38 Suppl. 1: 1–8
Lloyd T, Chinchilli VM, Eggli DF, et al. Body composition development of adolescent white females the Penn State Young Women’s Health Study. Arch Pediatr Adolesc Med 1998; 152: 998–1002
Martin AD, Bailey DA, McKay HA, et al. Bone mineral and calcium accretion during puberty. Am J Clin Nutr 1997; 66: 611–5
McKay HA, Bailey DA, Mirwald RL, et al. Peak bone mineral accrual and age at menarche in adolescent girls: a 6-year longitudinal study. J Pediatr 1998; 133: 682–7
Sundberg M, Gardsell P, Johnell O, et al. Pubertal bone growth in the femoral neck is predominantly characterized by increased bone size and not by increased bone density: a 4-year longitudinal study. Osteoporos Int 2003; 14: 548–58
Cadogan J, Blumsohn A, Barker ME, et al. A longitudinal study of bone gain in pubertal girls: anthropometric and biochemical correlates. J Bone Miner Res 1998; 13: 1602–12
Kannus P, Haapasalo H, Sankelo M, et al. Effect of starting age of physical activity on bone mass in the dominant arm of tennis and squash players. Ann Intern Med 1995; 123: 27–31
Katzman DK, Bachrach LK, Carter DR, et al. Clinical and anthropometric correlates of bone mineral acquisition in healthy adolescent girls. J Clin Endocrinol Metab 1991; 73: 1332–9
Lu PW, Briody JN, Ogle GD, et al. Bone mineral density of total body, spine, and femoral neck in children and young adults: a cross-sectional and longitudinal study. J Bone Miner Res 1994; 9: 1451–8
Kröger H, Kotaniemi A, Kröger L, et al. Development of bone mass and bone density of the spine and femoral neck: a prospective study of 65 children and adolescents. Bone Miner 1993; 23: 171–82
Matković V, Jelić T, Wardlaw GM, et al. Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model. J Clin Invest 1994; 93: 799–808
Mølgaard C, Thomsen BL, Prentice A, et al. Whole body bone mineral content in healthy children and adolescents. Arch Dis Child 1997; 76: 9–15
Tanner JM. Growth and maturation during adolescence. Nutr Rev 1981; 39: 43–55
Theintz G, Buchs B, Rizzoli R, et al. Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J Clin Endocrinol Metab 1992; 75: 1060–5
Bailey DA, McKay HA, Mirwald RL, et al. A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the University of Saskachewan bone mineral accrual study. J Bone Miner Res 1999; 14: 1672–9
Tanner JM, Whitehouse RH. Clinical longitudinal standards for heights, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1987; 51: 170–9
Nilsson O, Baron J. Fundamental limits on longitudinal bone growth: growth plate senescence and epiphyseal fusion. Trends Endocrinol Metab 2004; 15: 370–4
Hui SL, Wiske PS, Norton JA, et al. A prospective study of change in bone mass with age in postmenopausal women. J Chronic Dis 1982; 35: 715–25
Uusi-Rasi K, Sievanen H, Vuori I, et al. Associations of physical activity and calcium intake with bone mass and size in healthy women of different ages. J Bone Miner Res 1998; 13: 133–42
Krahl H, Michaelis U, Pieper H. -G, et al. Stimulation of bone growth through sports: a radiologic investigation of the upper extremities in professional tennis players. Am J Sports Med 1994; 22: 751–7
Haapasalo H, Kontulainen S, Sievanen H, et al. Exercise-induced bone gain is due to enlargement in bone size without a change in volumetric bone density: a peripheral quantitative computed tomography study of the upper arms of tennis players. Bone 2000; 27: 351–7
Gilsanz V, Boechat MI, Roe FF, et al. Gender differences in vertebral bone sizes in children and adolescents. Radiology 1994; 190: 673–7
Lloyd T, Rollings N, Andon MB, et al. Determinants of bone density in young women -I: relationships among pubertal development, total body bone mass, and total body bone density in premenarcheal females. J Clin Endocrinol Metab 1992; 75: 383–7
Bonjour JP, Theintz G, Buchs B, et al. Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. J Clin Endocrinol Metab 1991; 73: 555–63
Abrams SA, O’Brien KO, Stuff JE. Changes in calcium kinetics associated with menarche. J Clin Endocrinol Metab 1996; 81: 2017–20
Thomas KA, Cook SD, Bennett JT, et al. Femoral neck and lumbar spine bone mineral densities in a normal population 3–20 years of age. J Pediatr Orthop 1991; 11: 48–58
Gilsanz V, Gibbens DT, Carlson M, et al. Peak trabecular vertebral density: a comparison of adolescent and adult females. Calcif Tissue Int 1988; 43: 260–2
Shall S. Control of cell reproduction. Br Med Bull 1981; 37: 209–14
Karagiorgos A, Garcia JF, Brooks GA. Growth hormone response to continuous and intermittent exercise. Med Sci Sports 1979; 11: 302–7
Borer K. Exercise endocrinology. Champaign (IL): Human Kinetics, 2003
Holmes SJ, Skalet SM. Role of growth hormone and sex steroids in achieving and maintaining normal bone mass. Horm Res 1996; 45: 86–93
Johansson G, Bengtsson BA. Growth hormone and the acquisition of bone mass. Horm Res 1997; 48 Suppl. 5: 72–7
Froesch ER, Schmid C, Schwandes J, et al. Actions of insulin-like growth factors. Am J Physiol 1985; 47: 443–67
Spagnoli A, Rosenfeld RG. Insulin-like growth factor binding proteins. Curr Opin Endocrinol Diabetes 1997; 4: 1–9
Cornish J, Callon KE, Bava U, et al. Leptin directly regulates bone function in vitro and reduces bone fragility in vivo. J Endocrinol 2002; 175: 405–12
Canalis E. Effect of insulin-like growth factor I on DNA and protein synthesis in cultured rat calvaria. J Clin Invest 1980; 66: 709–19
Rodan SB, Weslowski G, Thomas K, et al. Growth stimulation of rat calvaria osteoblastic cells by acidic fibroblast growth factor. Endocrinology 1987; 121: 1917–23
Joyce ME, Jinguishi S, Bolander ME. Transforming growth factor-β in the regulation of fracture repair. Orthop Clin North Am 1990; 21: 199–209
Schmidt IU, Wakley GK, Turner RT. Effects of estrogen and progesterone on tibia histomorphometry in growing rats. Calcif Tissue Int 2000; 67: 47–52
Nilsson A, Ohlsson C, Isaksson OGP, et al. Hormonal regulation of longitudinal bone growth. Eur J Clin Nutr 1994; 48 Suppl. 1: S150–60
Kume K, Satomura K, Nishisho S, et al. Potential role of leptin in endochondral ossification. J Histochem Cytochem 2002; 50: 159–69
Scariano JK, Garry PJ, Montoya GD, et al. Serum leptin levels, bone mineral density and osteoblast alkaline phosphatase activity in elderly men and women. Mech Ageing Dev 2003; 124: 281–6
Dobing H, Turner RT. Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 1995; 136: 3632–8
Allain TJ, McGregor AM. Thyroid hormone and bone. J Endocrinol 1993; 139: 9–18
Chen HL, Demiralp B, Schneider A, et al. Parathyroid hormone and parathyroid hormone-related protein exert both pro- and anti-apoptotic effects in mesenchymal cells. J Biol Chem 2002; 277: 19374–81
Bellido T, Ali AA, Plotkin LI, et al. Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. J Biol Chem 2003; 278: 50259–72
Pereira RM, Delany AM, Canalis E. Cortisol inhibits the differentiation and apoptosis of osteoblasts in culture. Bone 2001; 28: 484–90
Barnard R, Ng KW, Martin TJ, et al. Growth hormone (GH) receptors in clonal osteoblast-like cells mediate a mitogenic response to GH. Endocrinology 1991; 128: 1459–64
Bando H, Zhang C, Takada Y, et al. Impaired secretion of growth hormone-releasing hormone, growth hormone and IGF-I in elderly men. Acta Endocrinol (Copenh) 1991; 124: 31–6
Clark RG, Jansson JO, Isaksson OGP, et al. Intravenous growth hormone: growth responses to patterned infusions in hypophysectomized rats. J Endocrinol 1985; 104: 53–61
Isgaard J, Carlsson L, Isaksson OGP, et al. Pulsatile intravenous growth hormone (GH) infusion to hypophysectomized rat increases insulin-like growth factor I messenger ribonucleic acid in skeletal tissues more effectively than continuous GH infusion. Endocrinology 1988; 123: 2605–10
Isgaard J, Moller C, Isaksson OGP, et al. Regulation of insulin- like growth factor I messenger ribonucleic acid in rat growth plate by growth hormone. Endocrinology 1988; 122: 1515–20
Maiter D, Underwood LE, Maes M, et al. Direct effect of intermittent and continuous growth hormone (GH) administration on serum somatomedin-C/insulin-like growth factor I and liver GH receptors in hypophysectomized rats. Endocrinology 1988; 123: 1053–9
Schwander JC, Hauri C, et al. Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: dependence on growth hormone status. Endocrinology 1983; 113: 297–305
Hall K, Brandt J, Enberg G, et al. Immunoreactive somatomedin A in human serum. J Clin Endocrinol Metab 1979; 48: 271–8
Amato G, Izzo GLA, Montagna G, et al. Low dose recombinant human growth hormone normalizes bone metabolism and cortical bone density and improves trabecular bone density in growth hormone deficient adults without causing adverse effects. Clin Endocrinol (Oxford) 1996; 45: 27–32
Bravenboer N, Holzmann P, De Boer H, et al. The effect of growth hormone (GH) on histomorphometric indices of bone structure and bone turnover in GH-deficient men. J Clin Endocrinol Metab 1997; 82: 1818–22
Wang DS, Sato K, Demura H, et al. Osteo-anabolic effects of human growth hormone with 22K- and 20K Daltons on human osteoblast-like cells. Endocr J 1999; 46: 125–32
Boguszewski CL, Jansson C, Boguszewski MC, et al. Circulating non-22 kDa growth homone isoforms in healthy children of normal stature: relation to height, body mass and pubertal development. Eur J Endocrinol 1997; 137: 246–53
Boguszewski CL, Jansson C, Boguszewski MC, et al. Increased proportion of circulating non-22-kilodalton growth hormone isoforms in short children: a possible mechanism for growth failure. J Clin Endocrinol Metab 1997; 82: 2944–9
Kostenuik PJ, Harris J, Halloran BP, et al. Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I. J Bone Miner Res 1999; 14: 21–31
Nishida S, Yamaguchi A, Tanizawa T, et al. Increased bone formation by intermittent parathyroid hormone administration is due to the stimulation of proliferation and differentiation of osteoprogenitor cells in bone marrow. Bone 1994; 15: 717–23
Hodsman AB, Fraher LJ, Ostbye T, et al. An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis. J Clin Invest 1993; 91: 1138–48
Schmidt IU, Dobnig H, Turner RT. Intermittent parathyroid hormone treatment increases osteoblast number, steady state messenger ribonucleic acid levels for osteocalcin, and bone formation in tibial metaphysis of hypophysectomized female rats. Endocrinology 1995; 136: 5127–34
Onyia JE, Bidwell J, Herring J, et al. In vivo, human parathyroid hormone fragment (pPTH 1–34) transiently stimulates immediate early response gene expression, but not proliferation, in trabecular bone cells of young rats. Bone 1995; 17: 479–84
Qin L, Raggatt LJ, Partridge NC. Parathyroid hormone: a double-edged sword for bone metabolism. Trends Endocrinol Metab 2004; 15: 60–5
Ohlsson C, Bengtsson BA, Isaksson OG, et al. Growth hormone and bone. Endocr Rev 1998; 19: 55–79
Russel-Aulet M, Shapiro B, Jaffe CA, et al. Peak bone mass in young healthy men is correlated with the magnitude of endogenous growth hormone secretion. J Clin Endocrinol Metab 1998; 83: 3463–8
Mora S, Pitukcheewanont P, Nelson JC, et al. Serum levels of insulin-like growth factor I and the density, volume, and cross-sectional area of cortical bone in children. J Clin Endocrinol Metab 1999; 84: 2780–3
Nindl BC, Scoville CR, Sheehan KM, et al. Gender differences in regional body composition and somatotrophic influences of IGF-I and leptin. J Appl Physiol 2002; 92: 1611–8
Sugimoto T, Nishiyama K, Kuribayashi F, et al. Serum levels of insulin-like growth factor (IGF)-I, IGF-binding protein (IGFBP)-2 and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res 1997; 12: 1272–9
Johansson AG, Forslund A, Hambraeus L, et al. Growth hormone-dependent insulin-like growth factor binding protein is a major determinant of bone mineral density in healthy men. J Bone Miner Res 1994; 9: 915–21
Koopmans SJ, de Boer SF, Sips HC, et al. Whole body and hepatic insulin action in normal, starved, and diabetic rats. Am J Physiol 1991; 260: E825–32
Fichter MM, Pirke KM. Effect of experimental and pathological weight loss upon the hypothalamo-pituitary-adrenal axis. Psychoneuroendocrinology 1986; 11: 295–305
Ketelslegers JM, Maiter D, Maes M, et al. Nutritional regulation of the growth hormone and insulin-like growth factor-binding proteins. Horm Res 1996; 45: 252–7
Thissen J, Underwood LE, Ketelslegers JM. Regulation of insulin-like growth factor-I in starvation and injury. Nutr Rev 1999; 57: 167–76
Hartman ML, Veldhuis JD, Johnson ML, et al. Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during two day fast in normal men. J Clin Endocrinol Metab 1992; 74: 757–65
Ho KY, Veldhuis JD, Johnson ML, et al. Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. J Clin Invest 1988; 81: 968–75
Iranmanesh A, Veldhuis JD. Clinical pathophysiology of the somatotropic (GH) axis in adults. Endocrinol Metab Clin North Am 1992; 21: 783–816
Nørrelund H, Nair KS, Nielsen S, et al. The decisive role of free fatty acids for protein conservation during fasting in humans with and without growth hormone. J Clin Endocrinol Metab 2003; 88: 4371–8
Schmid C, Ernst M. Insulin-like growth factors. In: Gowen M, editor. Cytokines and bone metabolism. Boca Raton (FL): CRC Press, 1992: 229–65
Marcus R, Cann C, Madvig P, et al. Menstrual function and bone mass in elite women distance runners: endocrine and metabolic features. Ann Intern Med 1985; 102: 158–63
Zanker CL, Swaine IL. Relation between bone turnover, oestradiol, and energy balance in women distance runners. Br J Sports Med 1998; 32: 167–71
Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–5
Maor G, Rochwerger M, Segev Y, et al. Leptin acts as a growth factor on the chondrocytes of skeletal growth centers. J Bone Miner Res 2002; 17: 1034–43
Gordeladze JO, Reseland JE. A unified model for the action of leptin on bone turnover. J Cell Biochem 2003; 88: 706–12
Grumbach MM. The neuroendocrinology of human puberty revisited. Horm Res 2002; 57 Suppl. 2: 2–14
Thomas T, Burguera B. Is leptin the link between fat and bone mass? J Bone Miner Res 2002; 17: 1563–9
Van Aggel-Leijssen DPC, Van Bak MA, Tennenbaum R, et al. regulation of average 24h human plasma leptin level: the influence of exercise and physiological changes in energy balance. J Obes Relat Metab Disord 1999; 23: 151–8
Kaufman BA, Warren MP, Dominguez JE, et al. Bone density and amenorrhea in ballet dancers are related to a decreased resting metabolic rate and lower leptin levels. J Clin Endocrinol Metab 2002; 87: 2777–83
Liesegang P, Romalo G, Sudmann M, et al. Human osteoblast-like cells contain specific, saturable, high-affinity glucocorticoid, androgen, estogen, and 1 alpha,25-dihydroxycholecalciferol receptors. J Androl 1994; 15: 194–9
Turner RT, Riggs BL, Spelsberg TC, et al. Skeletal effects of estrogen. Endocr Rev 1994; 15: 275–99
Compston JE, Laskey MA, Croucher PI, et al. Effect of diet-induced weight loss on total body bone mass. Clin Sci 1992; 82: 429–32
Williams GR, Robson H, Shalet SM. Thyroid hormone actions on cartilage and bone: interactions with other hormones at the epiphyseal plate and effects on linear growth. J Endocrinol 1998; 157: 823–7
Klein-Nulend J, Sterck JGH, Semeins CM, et al. Donor age and mechanosensitivity of human bone cells. Osteoporos Int 2002; 13: 137–46
Oscai LB, Spirakis CN, Wolff CA, et al. Effects of exercise and food restriction on adipose tissue cellularity. J Lipid Res 1971; 13: 588–90
Widdowson EM, McCance RA. Some effects of accelerating growth -I: general somatic development. Proc R Soc Lond B Biol Sci 1960; 24: 923–32
Caine D, Lewis R, O’Connor P, et al. Does gymnastics training inhibit growth of females? Clin J Sports Med 2001; 11: 260–70
Malina RM, Bouchard C. Growth, maturation and physical activity. Champaign (IL): Human Kinetics, 1991
Baxter-Jones ADG, Helms PJ. Effects of training at a young age: a review of the training of young athletes (TOYA) study. Pediatr Exer Sci 1996; 8: 310–27
Caine D, Bass SL, Daly R. Does elite competition inhibit growth and delay maturation in some gymnasts? Quite possibly. Pediatr Exer Sci 2003; 15: 360–72
Daly RM, Rich PA, Klein R, et al. Short stature in competitive prepubertal and early pubertal male gymnasts: The result of selection bias or intense training? J Pediatr 2000; 137: 510–6
Lindholm C, Hagenfeldt K, Ringertz BM. Pubertal development in elite juvenile gymnasts: effects of physical training. Acta Obstet Gynecol Scand 1994; 73: 269–73
Tveit-Milligan P, Spindler AA, Nichold JE. Genes and gymnastics: a case study of triplets. Sports Med Training Rehab 1993; 4: 47–52
Bass S, Bradney M, Pearce G, et al. Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts. J Bone Miner Res 1998; 13: 500–7
Jahreis G, Kauf E, Frohner G. Influence of intensive exercise on insulin-like growth factor I, thyroid and steroid hormones in female gymnasts. Growth Regul 1995; 1: 95–9
Theintz GE. Endocrine adaptation to intensive physical training during growth. Clin Endocrinol 1994; 41: 267–72
Smith WJ, Underwood L, Clemmons D. Effects of caloric or protein restriction on insulin-like growth factor I (IGF-I) and IGF-binding proteins in children and adults. J Clin Endocrinol Metab 1995; 80: 443–9
Bass S, Bradney M, Pearce G, et al. Short stature and delayed puberty in gymnasts: influence of selection bias on leg length and duration of training on trunk length. J Pediatr 2000; 136: 149–55
Constantini NW, Brautber C, Manny N, et al. Differences in growth and maturation in twin athletes. Med Sci Sports Exerc 1997; 29 Suppl. 5: S150
Warren MP. The effects of exercise on pubertal progression and reproductive function in girls. J Clin Endocrinol Metab 1980; 51: 279–94
Jacks DE, Sowash J, Anning J, et al. Effect of exercise at three exercise intensities on salivary cortisol. J Strength Cond Res 2002; 16: 286–9
Deuster PA, Petrides JS, Singh A, et al. High intensity exercise promotes escape of adrenocorticotropin and cortisol from suppression by dexamethasone: sexually dimorphic responses. J Clin Endocrinol Metab 1998; 83: 3332–8
De Souza MJ, Luciano AA, Arve JC, et al. Clinical tests explain blunted cortisol responsiveness but not mild hypercortisolism in amenorrheic runners. J Appl Physiol 1994; 76: 1302–9
Klingele KE, Kocher MS. Little league elbow: valgus overload injury in the paediatric athlete. Sports Med 2002; 15: 1005–15
Brot C, Jensen LB, Sorensen OH. Bone mass and risk factors for bone loss in perimenopausal Danish women. J Intern Med 1997; 242: 505–11
Ensrud KE, Ewing SK, Stone KL, et al. Weight loss in elderly women increases the risk of hip fracture irrespective of weight and weight loss intentions. J Bone Miner Res 2001; 16 Suppl. 1: S155
Hannan MT, Felson DT, Dawson-Hughes B, et al. Risk factors for longitudinal bone loss in elderly men and women: the Framingham osteoporosis study. J Bone Miner Res 2000; 15: 710–20
Mizuno K, Suzuki A, Ino Y, et al. Postmenopausal bone loss in Japanese women. Int J Gynaecol Obstet 1995; 50: 33–9
Ramsdale SJ, Bassey FJ. Changes in bone mineral density associated with dietary induced loss of body mass in young women. Clin Sci 1994; 87: 343–8
Svendsen OL, Hassager C, Christiansen C. Effect of an energy-restrictive diet with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women. Am J Med 1993; 95: 131–40
Edelstein SL, Barrett-Connor E. Relation between body size and bone mineral density in elderly men and women. Am J Epidemiol 1993; 138: 160–9
Ravn P, Hetland ML, Overgaard K, et al. Premenopausal and postmenopausal changes in bone mineral density of the proximal femur measured by dual-energy X-ray absorptiometry. J Bone Miner Res 1994; 9: 1975–80
Fall PM, Kennedy D, Smith JA, et al. Comparison of serum and urine assays for biochemical markers of bone resorption in postmenopausal women with and without hormone replacement therapy and in men. Osteoporos Int 2000; 11: 481–5
Ensrud KE, Lipschutz RC, Cauley JA, et al. Body size and hip fracture risk in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Am J Med 1997; 103: 274–80
Kushner FR, Kunigk A, Alspaugh M, et al. Validation of bioelectrical impedance analysis as a measurement of change in body composition in obesity. Am J Clin Nutr 1990; 52: 219–23
Weits T, van der Beek EJ, Wedel M, et al. Fat patterning during weight reduction: a multimode investigation. Neth J Med 1989; 35: 174–84
Westerterp KR, Saris WHM, Soeters PB, et al. Determinants of weight loss after vertical banded gastroplasty. Int J Obes 1991; 15: 529–34
Jensen LB, Quaade F, Sorensen OH. Bone loss accompanying voluntary weight loss in obese humans. J Bone Miner Res 1994; 9: 459–63
Cann CE, Martin MC, Genant HK, et al. Decreased spinal mineral content of amenorrheic women. JAMA 1984; 251: 626–9
Drinkwater BL, Nilson K, Chesnut III CH, et al. Bone mineral content of amenorrheic and eumenorrheic athletes. N Engl J Med 1984; 311: 277–81
Fisher EC, Nelson ME, Frontera WR, et al. Bone mineral content and levels of gonadotropins and estrogens in amenorrheic running women. J Clin Endocrinol Metab 1986; 62: 1232–6
Lindberg JS, Fears WB, Hunt MM, et al. Exercise-induced amenorrhea and bone density. Ann Intern Med 1984; 101: 647–8
Wilson JH, Wolman RL. Osteoporosis and fracture complications in an amenorrheic athlete. Br J Rheumatol 1994; 33: 480–1
Nichols DL, Sanborn CF, Bonnick SL, et al. The effects of gymnastics training on bone mineral density. Med Sci Sports Exerc 1994; 26: 1220–5
Okano H, Mizunuma H, Soda M, et al. Effects of exercise and amenorrhea on bone mineral density in teenage runners. J Endocrinol 1995; 42: 271–6
Myburgh KH, Hutchins J, Fataar AB, et al. Low bone density is an aetiologic factor for stress fractures in athletes. Ann Intern Med 1990; 113: 754–9
Rencken ML, Chesnut III CH, Drinkwater BL. Bone density at multiple skeletal sites in amenorrheic athletes. JAMA 1996; 276: 238–40
Loucks AB, Thuma JR. Luteinizing hormone pulsatility is disrupted at a threshold of energy availability in regularly menstruating women. J Clin Endocrinol Metab 2003; 88: 297–311
Loucks AB, Heath EM. Dietary restriction reduces luteinizing hormone (LH) pulse frequency during waking hours and increases LH pulse amplitude during sleep in young menstruating women. J Clin Endocrinol Metab 1994; 78: 910–5
Loucks AB, Verdun M, Heath EM. Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J Appl Physiol 1998; 84: 37–46
Hetland ML, Haarbo J, Christiansen C. Low bone mass and high bone turnover in male long distance runners. J Clin Endocrinol Metab 1993; 77: 770–5
Young N, Formica C, Szmuckler G, et al. Bone density at weight-bearing and nonweight bearing sites in ballet dancers: the effects of exercise, hypogonadism, and body weight. J Clin Endocrinol Metab 1994; 78: 449–54
Drinkwater BL, Bruemner B, Chesnut III CH. Menstrual history as a determinant of current bone density in young athletes. JAMA 1990; 263: 545–8
Drinkwater BL, Nilson K, Ott S, et al. Bone mineral density after resumption of menses in amenorrheic athletes. JAMA 1986; 256: 380–2
Keen AD, Drinkwater BL. Irreversible bone loss in former amenorrheic athletes. Osteoporos Int 1997; 7: 311–5
Gulekli B, Davies MC, Jacobs HS. Effect of treatment on established osteoporosis in young women with amenorrhea. Clin Endocrinol 1994; 41: 275–81
Haenggi W, Casez JP, Birkhaeuser MH, et al. Bone mineral density in young women with long-standing amenorrhea: limited effect of hormone replacement therapy with ethinylestradiol and desogestrel. Osteoporos Int 1994; 4: 99–103
Jonnavithula S, Warren MP, Fox RP, et al. Bone density is compromised in amenorrheic women despite return of menses: a 2-year study. Obstet Gynecol 1993; 81: 669–74
Warren MP, Brooks-Gunn J, Fox RP, et al. Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study. Fertil Steril 2003; 80: 398–404
Nelson ME, Meredith CN, Dawson-Hughes B, et al. Hormone and bone mineral status in endurance-trained and sedentary postmenopausal women. J Clin Endocrinol Metab 1988; 66: 927–33
Dawson-Hughes B, Shipp C, Sadowski L, et al. Bone density of the radius, spine and hip in relation to percent ideal body weight in postmenopausal women. Calcif Tissue Int 1987; 40: 310–4
Womersley J, Durnin JVGA, Boddy K, et al. Influence of muscular development, obesity, and age on the fat-free mass of adults. J Appl Physiol 1976; 41: 223–9
Foster GD, Wadden TA, Mullen JL, et al. Resting energy expenditure, body composition, and excess weight in the obese. Metabolism 1988; 37: 467–72
Longcope C, Pratt JH, Schneider SH, et al. Aromatization of androgens by muscle and adipose tissue in vivo. J Clin Endocrinol Metab 1978; 46: 146–52
Nimrod A, Ryan KJ. Aromatization of androgens by human abdominal and breast fat tissue. J Clin Endocrinol Metab 1975; 40: 367–72
Frisch RE, Canick JA, Tulchinsky D. Human fatty marrow aromatizes androgen to estrogen. J Clin Endocrinol Metab 1980; 51: 394–6
Nawata H, Tanaka S, Tanaka S, et al. Aromatase in bone cell: association with osteoporosis in postmenopausal women. J Steroid Biochem Mol Biol 1995; 53: 165–74
Institute of Medicine, National Academy of Sciences, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Food and Nutrition Board: dietary reference intakes for for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press, 1997
Alaimo K, McDowell MA, Breitel RR, et al. Dietary intake of vitamins, minerals, and fiber in persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, phase 1 1988–1991. Adv Data 1994 Nov 14; (258): 1–28
Eck LH, Hackett-Renner C. Calcium intake in youth: Sex, age, and racial differences in NHANES II. Prev Med 1992; 21: 473–82
Nicklas TA. Calcium intake trends and health consequences from childhood to adulthood. J Am Coll Nutr 2003; 22: 340–56
Looker AC, Harris TB, Madans JH, et al. Dietary calcium and hip fracture risk: the NHANES I epidemiologic follow-up study. Osteoporos Int 1993; 3: 177–84
Nordin B, Horsman A, Crilly R, et al. Treatment of spinal osteoporosis in postmenopausal women. BMJ 1980; 280: 451–4
Riggs B, Seeman E, Hodgson S, et al. Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis. N Engl J Med 1982; 306: 446–50
Bonjour JP, Carrie AL, Ferrari S, et al. Calcium-enriched foods and bone mass growth in prepubertal girls: a randomized, double-blind, placebo-controlled trial. J Clin Invest 1997; 99: 1287–94
Dibba B, Prentice A, Ceesay M, et al. Effect of calcium supplementation on bone mineral accretion in Gambian children accustomed to a low-calcium diet. Am J Clin Nutr 2000; 71: 544–9
Johnston Jr CC, Miller JZ, Slemenda CW, et al. Calcium supplementation and increases in bone mineral density in children. N Engl J Med 1992; 327: 82–7
Lee WT, Leung SS, Wang SH, et al. Double-blind, controlled calcium supplementation and bone mineral accretion in children accustomed to a low-calcium diet. Am J Clin Nutr 1994; 60: 744–50
Lee WT, Leung SS, Leung DM, et al. Bone mineral acquisition in low calcium intake children following the withdrawal of calcium supplement. Acta Paediatr 1997; 86: 570–6
Ruiz JC, Mandel C, Garabedian M. Influence of spontaneous calcium intake and physical exercise on the vertebral and femoral bone mineral density of children and adolescents. J Bone Miner Res 1995; 10: 675–82
Rozen GS, Rennert G, Rennert HS, et al. Calcium intake and bone mass development among Israeli adolescent girls. J Am Coll Nutr 2001; 20: 219–24
Lloyd T, Andon MB, Rollings N, et al. Calcium supplementation and bone mineral density in adolescent girls. JAMA 1993; 270: 841–4
Lloyd T, Martel JK, Rollings N, et al. The effect of calcium supplementation and Tanner stage on bone density, content and area in teenage women. Osteoporos Int 1996; 6: 276–83
Nowson CA, Green RM, Hopper JL, et al. A co-twin study of the effect of calcium supplementation on bone density during adolescence. Osteoporos Int 1997; 7: 219–25
Rozen GS, Rennert G, Dodiuk-Gad RP, et al. Calcium supplementation provides an extended window of opportunity for bone mass accretion after menarche. Am J Clin Nutr 2003; 78: 993–8
Baran D, Sorensen A, Grimes J, et al. Dietary modification with dairy products for preventing vertebral bone loss in premenopausal women: a three year prospective study. J Clin Endocrinol Metab 1990; 70: 264–70
Friedlander AL, Genant HK, Sadowsky S, et al. A two-year program of aerobic weight training enhances bone mineral density of young women. J Bone Miner Res 1995; 10: 574–85
Mazess RB, Barden HS. Bone density in premenopausal women: effects of age, dietary intake, physical activity, smoking, and birth-control pills. Am J Clin Nutr 1991; 53: 132–42
Freudenheim JL, Johnson NE, Smith EL. Relationships between usual nutrient intake and bone-mineral content of women 35–65 years of age: longitudinal and cross-sectional analysis. Am J Clin Nutr 1986; 44: 863–76
Rus B, Thomsen K, Christiansen C. Does calcium supplementation prevent postmenopausal bone loss? N Engl J Med 1991, 177
Smith EL, Gilligan C, Smith PE, et al. Calcium supplementation and bone loss in middle-aged women. Am J Clin Nutr 1989; 50: 833–42
Elders PJM, Netelenbos JC, Lips P, et al. Calcium supplementation reduces vertebral bone loss in perimenopausal women: a controlled trial in 248 women between 46 and 55 years of age. J Clin Endocrinol Metab 1991; 73: 53–540
Cumming RG. Calcium intake and bone mass: a quantitative review of the evidence. Calcif Tissue Int 1990; 47: 194–201
Welten DC, Kemper HCG, Post GB, et al. A meta-analysis of the effect of calcium intake on bone mass in young and middle aged females and males. J Nutr 1995; 125: 2802–13
Dhonukshe-Rutten RAM, Lips M, deJong N, et al. Vitamin B-12 status is associated with bone mineral content and bone mineral density in frail elderly women but not in men. J Nutr 2003; 133: 801–7
Macdonald HM, New SA, Golden MHN. Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of detrimental effect of fatty acids. Am J Clin Nutr 2004; 79: 155–65
Blimkie CJR, Rice S, Webber CE, et al. Effects of resistance training on bone mineral content and density in adolescent females. Can J Physiol Pharmacol 1996; 74: 1025–103
Mei J, Yeung SSC, Kung AWC. High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 2001; 86: 5217–21
New SA, MacDonald H, Campbell MK, et al. Lower estimates of net endogenous noncarbonic acid production are positively associated with indexes of bone health in premenopausal and perimenopausal women. Am J Clin Nutr 2004; 79: 131–8
Hert J, Liskova M, Landa J. Reaction of bone to mechanical stimuli I: continuous and intermittent loading of tibia in rabbit. Folia Morphol (Praha) 1971; 19: 290–300
Lanyon LE, Rubin CT. Static vs dynamic loads as a stimulus for bone remodeling. J Biomech 1984; 15: 767–81
Liskova M, Hert J. Reaction of bone to mechanical stimuli: Part 2. periosteal and endosteal reaction to tibial diaphysis in rabbit to intermittent loading. Folia Morphol (Praha) 1971; 19: 301–17
Rubin CT, Lanyon LE. Regulation of bone formation by applied dynamic loads. J Bone Joint Surg 1984; 66A: 397–402
Duncan CS, Blimkie CJR, Cowell CT, et al. Bone mineral density in adolescent female athletes: relationship to exercise type and muscle strength. Med Sci Sports Exerc 2002; 34: 286–94
Fuchs RK, Bauer JJ, Snow CM. Jumping improves hip and lumbar spine bone mass in prepubescent children: a randomized controlled trial. J Bone Miner Res 2001; 16: 148–56
Fuchs RK, Snow CM. Gains in hip bone mass from high-impact training are maintained: a randomized controlled trial in children. J Pediatr 2002; 141: 357–62
Laing EM, Massoni JA, Nichols-Richardson SM, et al. A prospective study of bone mass and body composition in female adolescent gymnasts. J Pediatr 2002; 141: 211–6
Haapasalo H, Kannus P, Sievanen H, et al. Effect of long-term unilateral activity on bone mineral density of female junior tennis players. J Bone Miner Res 1998; 13: 310–9
Heinonen A, Sievänen H, Kannus P, et al. High-impact exercise and bones of growing girls: a 9-month controlled trial. Osteoporos Int 2000; 11: 1010–7
MacKelvie KJ, McKay HA, Khan KM, et al. A school-based exercise intervention augments bone mineral accrual in early pubertal girls. J Pediatr 2001; 139: 501–8
McKay HA, Petit MA, Schutz RW, et al. Augmented trochanteric bone mineral density after modified physical education classes: a randomized school-based exercise intervention study in prepubescent and pubescent children. J Pediatr 2000; 136: 156–62
Morris FL, Naughton GA, Gibbs JL, et al. Prospective ten-month exercise intervention in premenarcheal girls: positive effects on bone and lean mass. J Bone Miner Res 1997; 12: 1453–62
Nichols DL, Sanborn CF, Love AM. Resistance training and bone mineral density in adolescent females. J Pediatr 2001; 139: 494–500
Petit MA, McKay HA, MacKelvie KI, et al. A randomized school-based jumping intervention confers site and maturity-specific benefits on bone structural properties in girls: a hip structural analysis study. J Bone Miner Res 2002; 17: 363–72
Slemenda CW, Reister TK, Hui SL, et al. Influences on skeletal mineralization in children and adolescents: evidence for varying effects of sexual maturation and physical activity. J Pediatr 1994; 125: 210–07
Helge EW, Kanstrup I-L. Bone density in female elite gymnasts: impact of muscle strength and sex hormones. Med Sci Sports Exerc 2002; 34: 174–80
Taafe DR, Snow-Harter C, Connolly DA, et al. Differential effects of swimming versus weight-bearing activity on bone mineral status of eumenorrheic athletes. J Bone Miner Res 1995; 10: 586–93
Kontulainen S, Kannus P, Haapasalo H, et al. Good maintenance of exercise-induced bone gain with decreased training of female tennis and squash players: a prospective 5-year follow-up study of young and old starters and controls. J Bone Miner Res 2001; 16: 195–201
Talmage RV, Stinnett SS, Landwehr JT, et al. Age-related loss of bone mineral density in non-athletic and athletic women. Bone Miner 1986; 1: 115–25
Haapasalo H, Kannus P, Sievanen H, et al. Long-term unilateral loading and bone mineral density in female squash players. Calcif Tissue Int 1994; 54: 249–55
Heinonen A, Sievänen H, Kannus P, et al. Effects of unilateral strength training and detraining on bone mineral mass and estimated mechanical characteristics of the upper limb bones in young women. J Bone Miner Res 1996; 11: 490–501
Heinonen A, Oja P, Kannus P, et al. Bone mineral density in female athletes representing sports with different loading characteristics of the skeleton. Bone 1995; 17: 197–203
Taaffe DR, Robinson TL, Snow CM, et al. High-impact exercise promotes bone gain in well-trained female athletes. J Bone Miner Res 1997; 12: 255–60
Fehling PC, Alekel L, Clasey J, et al. A comparison of bone mineral densities among female athletes in impact loading and active loading sports. Bone 1995; 17: 205–10
Wolman RL, Fauman L, Clark P, et al. Different training patterns and bone mineral density of the femoral shaft in elite, female athletes. Ann Rheum Dis 1991; 50: 487–9
Creighton DL, Morgan AL, Boardley D, et al. Weight-bearing exercise and markers of bone turnover in female athletes. J Appl Physiol 2001; 90: 565–70
Heinonen A, Oja P, Kannus P, et al. Bone mineral density of female athletes in different sports. Bone Miner 1993; 23: 1–14
Snow-Harter C, Bouxsein ML, Lewis BT, et al. Effects of resistance and endurance exercise on bone mineral status of young women: a randomized exercise intervention trial. J Bone Miner Res 1992; 7: 761–9
Kirk S, Sharp CF, Elbaum N, et al. Effect of long distance running on bone mass in women. J Bone Miner Res 1989; 4: 515–22
Alekel L, Clasey JL, Fehling PC, et al. Contributions of exercise, body composition, and age to bone mineral density in premenopausal women. Med Sci Sports Exerc 1995; 27: 1477–85
Winters KM, Snow CM. Detraining reverses positive effects of exercise on the musculoskeletal system in premenopausal women. J Bone Miner Res 2000; 15: 2495–503
Orwoll ES, Ferar J, Oviatt SK, et al. The relationship of swimming exercise to bone mass in men and women. Arch Intern Med 1999; 149: 2197–200
Notelovitz M, Martin D, Tesar R, et al. Estrogen therapy and variable-resistance weight training increase bone mineral in surgically menopausal women. J Bone Miner Res 1991; 6: 583–90
Pocock NA, Eisman JA, Yeates MG, et al. Physical fitness is a major determinant of femoral neck and lumbar spine bone mineral density. J Clin Invest 1986; 78: 618–21
Aloia JF, Cohn SH, Ostuni JA, et al. Prevention of involutional bone loss by exercise. Ann Intern Med 1978; 89: 356–8
Brewer V, Meyer BM, Keele MS, et al. Role of exercise in prevention of involutional bone loss. Med Sci Sports Exerc 1983; 15: 445–9
Aloia JF, Waswani AN, Yeh JK, et al. Postmenopausal bone mass is related to physical activity. Arch Intern Med 1988; 148: 121–3
Zhang J, Feldblum PJ, Fortnej JA. Moderate physical activity and bone density among perimenopausal women. Am J Public Health 1992; 82: 736–8
Sowers M, Crutchfield M, Bandekar R, et al. Bone mineral density and its change in pre- and perimenopausal white women: the Michigan Health Study. J Bone Miner Res 1998; 13: 1134–40
Sowers MR, Greendale GA, Bondarenko I, et al. Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN. Osteoporos Int 2003; 14: 191–7
Sowers MR, Finkelstein JS, Ettinger B, et al. The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN. Osteoporos Int 2003; 14: 44–52
Heaney RP. Estrogen-calcium interactions in the postmenopause: a quantitative description. Bone Miner 1990; 11: 67–84
Mazess RB, Barden H. Bone density of the spine and femur in adult white females. Calcif Tissue Int 1999; 65: 91–9
Sowers MR, Clark M, Hollis B, et al. Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss. J Bone Miner Res 1992; 7: 647–57
Baran DT. Magnitude and determinants of premenopausal bone loss. Osteoporos Int 1994; S1: S31–4
Lofman O, Larsson L, Ross L, et al. Bone mineral density in normal Swedish women. Bone 1997; 20: 167–74
Recker RR, Lappe JM, Davies M, et al. Change in bone mass immediately before menopause. J Bone Miner Res 1992; 7: 857–62
Riggs BL, Wehner HW, Dunn WL, et al. Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest 1981; 67: 328–35
Riggs BL, Wehner HW, Melton J, et al. Rates of bone loss in the appendicular and axial skeletons of women. J Clin Invest 1986; 77: 1487–91
Lindsay R, Hart DM, Aitkin JM, et al. Long-term prevention of osteoporosis by oestrogen: evidence for an increased bone mass after delayed onset of treatment. Lancet 1976; I: 1038–41
Lindsay R, Maclean A, Kraszewski A, et al. Bone response to termination of estrogen treatment. Lancet 1978; I: 1325–7
Nordin BE, Need AG, Chatterton BE, et al. The relative contributions of age and years since menopause to postmenopausal bone loss. J Clin Endocrinol Metab 1990; 70: 83–8
Recker RR, Saville PD, Heany RP. Effect of estrogens and calcium carbonate on bone loss in postmenopausal women. Ann Intern Med 1977; 87: 649–55
Slemenda CW, Hui SL, Longcope C, et al. Sex steroids and bone mass. J Clin Invest 1987; 80: 1261–9
Slemenda CW, Longcope C, Peacock M, et al. Sex steroids, bone mass, and bone loss: a prospective study of pre-, peri and postmenopausal women. J Clin Invest 1996; 97: 14–21
Atkinson PJ. Changes in resorption spaces in femoral cortical bone with age. J Pathol Bacteriol 1965; 89: 173–6
Peacock M, Liu G, Carey M, et al. Bone mass and structure at the hip in men and women over the age of 60 years. Osteoporos Int 1998; 8: 231–9
Bousson V, Meunier A, Bergot C, et al. Distribution of intracortical porosity in human midfemoral cortex by age and gender. J Bone Miner Res 2001; 16: 1308–17
Aaron JE, Makins NB, Sagreiya K. The microanatomy of trabecular bone loss in normal aging men and women. Clin Orthop 1987; 215: 260–71
Atkinson PJ. Variation in trabecular structure of vertebrae with age. Calcif Tissue Res 1967; 1: 24–32
Aaron JE, Shore PA, Shore RC, et al. Trabecular architecture in women and men of similar bone mass with and without vertebral fracture -II: three-dimensional histology. Bone 2000; 27: 277–82
Dempster DM. The contribution of trabecular architecture to cancellous bone quality. J Bone Miner Res 2000; 15: 20–3
Rudman D, Kutner MH, Rogers CM, et al. Impaired growth hormone secretion in the adult population. J Clin Invest 1981; 67: 1361–9
Veldhuis JD, Iranmanesh A, Lizzaralde G, et al. Combined deficits in the somatoropic and gonadotropic axes in healthy older men: an appraisal of neuroendocrine mechanisms by deconvolution analysis. Neurobiol Aging 1994; 15: 509–17
Rico H, Del Rio A, Vila T, et al. The role of growth hormone in postmenopausal osteoporosis. Arch Intern Med 1979; 139: 1263–5
Johansson AG, Burman P, Westermark K, et al. The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I. J Intern Med 1992; 232: 447–52
Romagnoli E, Minisola S, Carnevale V, et al. Effect of estrogen deficiency on IGF-I plasma levels: relationship with bone mineral density in perimenopausal women. Calcif Tissue Int 1993; 53: 1–6
Wuster C, Blum WF, Schlemilch S, et al. Decreased serum levels of insulin-like growth factors and IGF binding protein 3 in osteoporosis. J Intern Med 1993; 234: 249–55
Ravn P, Overgaaerd K, Spencer EM, et al. Insulin-like growth factors I and II in healthy women with and without established oseoporosis. Eur J Endocrinol 1995; 132: 313–9
Reed BY, Serwekh JE, Sakhee K, et al. Serum IGF-I is low and correlated with osteoblastic surface in idiopathic osteoporosis. J Bone Miner Res 1995; 10: 1218–24
Boonen S, Lesaffre E, Dequeker J, et al. Relationship between baseline insulin-like growth factor-I (IGF-I) and femoral bone density in women aged over 70 years: potential implications for the prevention of age-related bone loss. J Am Geriatr Soc 1996; 44: 1301–6
Kurland ES, Rosen CJ, Cosman F, et al. Insulin-like growh factor-I in men with idiopathic ostoporosis. J Clin Endocrinol Metab 1997; 82: 2799–805
Fall C, Hindmarsh P, Dennison E, et al. Programming of growth hormone secretion and bone mineral density in elderly men: a hypothesis. J Clin Endocrinol Metab 1998; 83: 135–9
Barrett-Connor E, Goodman-Gruen D. Gender differences in insulin-like growth factor and bone mineral density association in old age: the Rancho Bernardo Study. J Bone Miner Res 1998; 13: 1343–9
Langlois JA, Rose CJ, Visser M, et al. Association between insuilin-like growth factor I and bone mineral density in older women and men: the Framingham Heart Study. J Clin Endocrinol Metab 1998; 83: 4257–62
Seck T, Scheidt-Nave C, Leidig-Bruckner G, et al. Low serum concentrations of insulin-like growth factor are associated with femoral bone loss in a population-based sample of postmenopausal women. Clin Endocrinol 2001; 55: 101–6
Vestergaard P, Hermann AP, Orskov H, et al. Effect of sex hormone replacement on the insulin-like growth factor system and bone mineral: a cross-sectional and longitudinal study in 595 perimenopausal women participating in the Danish Osteoporosis Prevention Study. J Clin Endocrinol Metab 1999; 84: 2286–90
Scheidt-Nave C, Bismar H, Leidig-Bruckner G, et al. Serum interleukin-6 is a major predictor of bone loss in women specific to the first decade past menopause. J Bone Miner Res 1999; 14: 1057
Blain H, Vuillemin A, Guillemin F, et al. Serum leptin level is a predictor of bone mineral density in postmenopausal women. J Clin Endocrinol Metab 2002; 87: 1030–5
Yamauchi M, Sugimoto T, Yamaguchi T, et al. Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol 2001; 55: 341–7
Zoico E, Zamboni M, Adami S, et al. Relationship between leptin levels and bone mineral density in the elderly. Clin Endocrinol 2003; 59: 97–103
Blum M, Harris SS, Must A, et al. Leptin, body composition and bone mineral density in premenopausal women. Calcif Tissue Int 2003; 73: 27–32
Ruhl CE, Everhart JE. Relationship of serum leptin concentration with bone mineral density in the United States population. J Bone Miner Res 2002; 17: 1896–903
Sato M, Takeda N, Sarui H, et al. Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab 2001; 86: 5273–6
Thomas T. Leptin: a potential mediator for protective effects of fat mass on bone tissue. Joint Bone Spine 2003; 70: 18–21
Whitfield JF. Leptin: brains and bones. Expert Opin Investig Drugs 2001; 10: 1617–22
Zofkova I, Rojdmark S, Kancheva RL. Does estrogen replacement therapy influence parathyroid hormone responsiveness to exogenous hypercalcemia in postmenopausal women? J Endocrinol Invest 1993; 16: 323–7
Vincent A, Riggs BL, Atkinson EJ, et al. Effect of estrogen replacement therapy on parathyroid hormone secretion in elderly postmenopausal women. Menopause 2003; 10: 165–71
Taxel P, Fall PM, Albertsen PC, et al. The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer. J Clin Endocrinol Metab 2002; 87: 4907–13
Whitehead MI, Lane G, Townsend PT, et al. Effects in postmenopausal women of natural and synthetic estrogens on calcitonin and calcium-regulating hormone secretion: relevance to postmenopausal osteoporosis. Acta Obstet Gynecol Scand Suppl 1981; 106: 27–32
Ten Bolscher M, Netelenbos JC, Barto R, et al. Estrogen regulation of intestinal calcium absorption in the intact and ovariectomized adult rat. J Bone Miner Res 1999; 14: 1197–202
Kalu DN, Chen C. Ovariectomized murine model of postmenopausal calcium malabsorption. J Bone Miner Res 1999; 14: 593–601
Arjmandi BH, Hollis BW, Kalu DN. In vivo effect of 17 beta-estradiol on intestinal calcium absorption in rats. Bone Miner 1994; 26: 181–9
McKane WR, Khosla S, Burritt MF, et al. Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause: a clinical research center study. J Clin Endocrinol Metab 1995; 80: 3458–64
Uemura H, Irahara M, Yoneda N, et al. Close correlation between estrogen treatment and renal phosphate reabsorption capacity. J Clin Endocrinol Metab 2000; 85: 1215–9
van Hoof HJ, van der Mooren MJ, Swinkels LM, et al. Hormone replacement therapy increases serum 1,25-dihydroxyvitamin D: a 2-year prospective study. Calcif Tissue Int 1994; 55: 417–9
Liel Y, Shany S, Smirnoff P, et al. Estrogen increases 1,25-dihydroxyvitamin D receptor expression and bioresponse in the rat duodenal mucosa. Endocrinology 1999; 140: 280–5
Breslau N. Calcium homeostasis. In: Griffin JE, Ojeda SR. Textbook of endocrine physiology. 3rd ed. Oxford: Oxford University Press, 1996: 316
Farrach-Carson MC, Ridal AL. Dual 1,25(OH)-dihydroxyvitamin D3 signal response pathways in osteoblasts: cross talk between genomic and membrane initiated pathways. Am J Kidney Dis 1998; 31: 729–42
Adami S, Gatti D, Bertoldo F, et al. The effects of menopause and estrogen replacement therapy on the renal handling of calcium. Osteoporos Int 1992; 2: 180–5
Slovik DM, Adams JS, Neer RM, et al. Deficient production of 1,25-dihydroxyvitamin D in elderly osteoporotic patients. N Engl J Med 1981; 305: 372–4
Khosla S, Atkinson EJ, Melton III LJ, et al. Effects of age and estrogen status on serum parathyroid hormone levels and biochemical markers of bone turnover in women: a population-based study. J Clin Endocrinol Metab 1997; 82: 1522–7
Kotowicz MA, Klee GG, Kao PC, et al. Relationship between serum intact parathyroid hormone concentrations and bone remodeling in type I osteoporosis: evidence that skeletal sensitivity is increased. Osteoporos Int 1990; 1: 14–22
Sirola J, Kroger H, Honkanen R, et al. Risk factors associated with peri- and postmenopausal bone loss: does HRT prevent weight-loss related bone loss? Osteoporos Int 2003; 14: 27–33
Cifuentes M, Johnson MA, Lewis RD, et al. Bone turnover and body weight relationships differ in normal-weight compared to heavier postmenopausal women. Osteoporos Int 2003; 14: 116–22
Dawson-Hughes B, Dallal GE, Krall EA, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990; 323: 878–83
Heaney RP. Calcium, bone health, and osteoporosis. Bone Miner Res 1986; 4: 255–301
Riis B, Thomsen K, Christiansen C. Does calcium supplementation prevent postmenopausal bone loss? N Engl J Med 1987; 316: 173–7
Prince RL, Smith M, Dick IM, et al. Prevention of postmenopausal osteoporosis: a comparative study of exercise, calcium supplementation, and hormone-replacement therapy. N Engl J Med 1991; 325: 1189–95
Horsman A, Gallagher JC, Simpson M, et al. Prospective trial of oestrogen and calcium in postmenopausal women. BMJ 1977; 2: 789–92
Heikkinen J, Kyllonen E, Kurttila-Matero E, et al. HRT and exercise: Effects on bone density, muscle strength and lipid metabolism: a placebo controlled 2-year prospective trial on two estrogen-progestin regimens in healthy postmenopausal women. Maturitas 1997; 26: 139–49
Reid IR, Ames RW, Evans MC, et al. Effects of calcium supplementation on bone loss in postmenopausal women. N Engl J Med 1993; 328: 460–4
Heaney RP, Recker RR, Saville PD. Menopausal changes in calcium balance performance. J Lab Clin Med 1978; 92: 953–63
Prince R, Devine A, Dick I, et al. The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women. J Bone Miner Res 1995; 10: 1068–75
Specker BL. Evidence for an interaction between calcium intake and physical activity on changes in bone mineral density. J Bone Miner Res 1996; 11: 1539–44
Bloomfield SA, Williams NI, Lamb DR, et al. Non-weight bearing exercise may increase spine bone mineral density in healthy postmenopausal women. Am J Phys Med Rehabil 1993; 72: 204–9
Kohrt WM, Snead DB, Slatopolsky E, et al. Additive effects of weight-bearing exercise and estrogen on bone mineral density in older women. J Bone Miner Res 1995; 10: 1303–11
Heaney RP, Dowell MS, Hale CA, et al. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 2003; 22: 142–6
Smith E, Smith P, Ensign C, et al. Bone involution decrease in exercising middle aged women. Calcif Tissue Int 1984; 36: S129–38
Sinaki M, Mikkelsen BA. Postmenopausal spinal osteoporosis: flexion versus extension exercises. Arch Phys Med Rehabil 1984; 65: 593–6
Etherington J, Harri PA, Nandra D, et al. The effect of weight-bearing exercise on bone mineral density: a study of female ex-elite athletes and general population. J Bone Miner Res 1996; 11: 1333–8
Hatori M, Hasegawa A, Adachi H, et al. The effects of walking at the anaerobic threshold level on vertebral bone loss in postmenopausal women. Calcif Tissue Int 1993; 52: 411–4
Martin D, Notelovitz M. Effects of aerobic training on bone mineral density of postmenopausal women. J Bone Miner Res 1993; 8: 931–6
Preisinger E, Alacamlioglu Y, Pils K, et al. Therapeutic exercise in the prevention of bone loss: a controlled trial with women after menopause. Am J Phys Med Rehabil 1995; 74: 120–3
Bravo G, Gauthier P, Roy PM, et al. Impact of a 12-month exercise program on the physical and psychological health of osteopenic women. J Am Geriatr Soc 1996; 44: 756–62
Hartard M, Haber P, Ilieva D, et al. Systematic strength training as a model of therapeutic intervention. Am J Phys Med Rehabil 1996; 75: 21–8
Pruitt LA, Taaffe DR, Marcus R. Effects of one-year high-intensity versus low-intensity resistance training program on bone mineral density in older women. J Bone Miner Res 1995; 10: 1788–95
Kraemer WJ, Fleck SJ, Dziados JE, et al. Changes in hormonal concentrations after different heavy resistance exercise protocols in women. J Appl Physiol 1993; 75: 594–604
Heinonen A, Kannus P, Sievanen H, et al. Randomised controlled trial of effect of high-impact exercise on selected risk factors for osteoporotoic fractures. Lancet 1996; 348: 1343–7
Weltman A, Pritzlaff CJ, Wideman L, et al. Exercise-dependent growth hormone release is linked to markers of heightened central adrenergic outflow. J Appl Physiol 2000; 89: 629–35
Kraemer WJ, Anguillera BA, Terada M, et al. Responses of IGF-I to endogenous increases in growth hormone after heavy resistance exercise. J Appl Physiol 1995; 79: 1310–5
Baker ER, Mathur RS, Kirk RF, et al. Plasma gonadotropins, prolactin, and steroid hormone concentrations in female runners immediately after a long-distance run. Fertil Steril 1982; 38: 38–41
Tsai KS, Lin JC, Chen CK, et al. Effect of exercise and exogenous glucocorticoid on serum level of intact parathyroid hormone. Int J Sports Med 1997; 18: 583–7
Sutton JR, Lazarus L. Growth hormone in exercise: comparison of physiologic and pharmacologic stimuli. J Appl Physiol 1976; 41: 523–7
VanHelder WP, Goode RC, Radomski MW. Effect of anaerobic and aerobic exercise of equal duration and work expenditure on plasma growth hormone levels. Eur J Appl Physiol 1984; 52: 255–7
Craig BW, Brown R, Everhart J. Effects of progressive resistance training on growth hormone and testosterone levels in young and elderly subjects. Mech Ageing Dev 1989; 49: 159–69
Poehlman ET, Rosen CJ, Copeland KC. The influence of endurance training on insulin-like growth factor-I in older individuals. Metabolism 1994; 43: 1401–5
Frost HM. Bone ‘mass’ and the ‘mechanostat’: a proposal. Anat Rec 1987; 219: 1–9
Frost HM. The mechanostat: a proposed pathogenic mechanism of osteoporosis and the bone mass effects of mechanical and nonmechanical agents. Bone Miner 1987; 2: 73–86
Frost HM. Suggested fundamental concepts in skeletal physiology. Calcif Tissue Int 1993; 52: 1–4
Lanyon LE. Functional strain in bone as an objective and controlling stimulus for the adaptive bone remodeling. J Biomech 1987; 20: 1083–93
Rubin CT, Lanyon LE. Regulation of bone mass by mechanical strain magnitude. Calcif Tissue Int 1985; 37: 411–7
Turner CH. Homeostatic control of bone structure: an application of feedback theory. Bone 1991; 12: 203–17
Nilsson J, Thorstensson A. Ground reaction forces at different speeds of humans walking and running. Acta Physiol Scand 1989; 136: 217–27
Bergmann G, Graichen F, Rohlmann A. Hip joint loading during walking and running, measured in two patients. J Biomech 1993; 26: 969–90
Bergmann G, Graichen F, Rohlmann A. Is staircase walking a risk for the fixation of hip implants? J Biomech 1995; 28 (5): 535–53
Kotzar GM, Davy DT, Goldberg VM, et al. Telemeterized in vivo hip joint force data: a report on two patients after total hip surgery. J Orthop Res 1991; 9: 621–33
Davy DT, Kotzar GM, Brown RH, et al. Telemetric force measurements across the hip after total arthroplasty. J Bone Joint Surg 1988; 70: 45–50
Breit GA, Whalen RT. Prediction of human gait parameters from temporal measures of foot-ground contact. Med Sci Sport Exerc 1997; 29: 540–7
Cavanagh PR, Lafortune MA. Ground reaction forces in distance running. J Biomech 1980; 13: 397–406
Munro CF, Miller DI, Fuglevand AJ. Ground reaction forces in running: a reexamination. J Biomech 1987; 20: 147–55
Winter DA. The biomechanics and motor control of human gait. Waterloo (ON): University of Waterloo Press, 1987: 1–296
Hsieh Y-F, Turner CH. Effects of loading frequency on mechanically induced bone formation. J Bone Miner Res 2001; 16: 918–24
Rubin CT, McLeod KJ. Promotion of bony ingrowth by frequency-specific, low-amplitude mechanical strain. Clin Orthop Relat Res 1994; 198: 165–74
Rubin J, Murphy T, Fan X, et al. Mechanical strain inhibits RANKL expression through activation of ERK 1/2 in bone marrow cells. J Bone Miner Res 2002; 17: 1452–60
Rubin C, Turner AS, Mallinckrodt C. Mechanical strain, induced noninvasively in the high-frequency domain, is anabolic to cancellous bone, but not cortical bone. Bone 2002; 30: 445–52
Robling AG, Burr DB, Turner CH. Partitioning a daily mechanical stimuous into discrete loading bouts improves the osteogenic response to loading. J Bone Miner Res 2000; 15: 1596–602
Robling AG, Burr DB, Turner CH. Recovery periods restore mechanosensitivity to dynamically loaded bone. J Exp Biol 2001; 204: 3389–99
Robling AG, Hinant FM, Burr DB, et al. Improved bone structure and strength after short-term mechanical loading is greatest if loading is separated into short bouts. J Bone Miner Res 2002; 17: 1545–54
Robling AG, Hinant FM, Burr DB, et al. Shorter, more frequent mechanical loading sessions enhance bone mass. Med Sci Sports Exer 2002; 34: 196–202
Umemura Y, Ishiko T, Yamauchi T, et al. Five jumps per day increase bone mass and breaking force in rats. J Bone Miner Res 1997; 12: 1480–5
Turner CH, Robling AG. Designing exercise regimens to increase bone strength. Med Sci Sports Exerc 2003; 31: 45–50
Lanyon LE, Goodship AE, Pye CJ, et al. Mechanically adaptive bone remodeling: a quantitative study on functional adaptation in the radius following ulna osteotomy in sheep. J Biomech 1982; 15: 141–54
Lanyon LE. Bone loading: the functional determinant of bone architecture and physiological contributor to the prevention of osteoporosis. In: Smith R, editor. Osteoporosis. London: LR Printing Services Ltd, 1990: 63
Eaton SB, Eaton SB. An evolutionary perspective on human physical activity: implications for health. Comp Biochem Physiol A Mol Integr Physiol 2003; 136: 153–9
Acknowledgements
The author thanks Dr Steven Goldstein and Dr MaryFran Sowers for comments that helped improve the manuscript, and Mrs Jean Hunt for skillful drafting of figure 3. No sources of funding were used to assist in the preparation of this review. The author has no conflicts of interest that are directly relevant to the content of this review.
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Borer, K.T. Physical Activity in the Prevention and Amelioration of Osteoporosis in Women. Sports Med 35, 779–830 (2005). https://doi.org/10.2165/00007256-200535090-00004
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DOI: https://doi.org/10.2165/00007256-200535090-00004