Disorders of Skeletal Aging

  • Diane Meier


Skeletal pathology is a leading cause of serious morbidity and functional loss in old age. However, it is difficult to distinguish between disease and normal age changes in the clinical approach to bone disorders, and this has lead to substantial controversy over the diagnosis and treatment of the most common metabolic bone disease, osteoporosis. For example, loss of skeletal calcium is a nearly universal concomitant of aging, independent of body size, race, or gender, but the process does not become pathologic until it is of sufficient magnitude to lead to osteoporotic fracture, with associated adverse consequences such as pain, immobility, deformity, and (in the case of hip fracture) premature death. Defining the point at which these age-related skeletal changes require intervention presents a major challenge to researchers and clinicians alike. Reasons for these difficulties include the fact that there is a long latent period of bone loss before the onset of clinically apparent disease, that current diagnostic procedures are unable to separate those at risk of fracture from those not at risk, that available treatment modalities have not been subject to randomized long-term study, and in particular, that studies of treatments for older adults are almost completely lacking. Research efforts directed at these issues have increased dramatically as a result of demographic changes leading to a large aging female population at high risk for osteoporosis and because of rapidly developing technologies in the measurement of bone mineral content.


Bone Loss Bone Mass Vertebral Fracture Endometrial Cancer Osteoporotic Fracture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Riggs BL, Melton LJ III. Involutional osteoporosis. N Engl J Med 1986; 314: 1676–86.CrossRefPubMedGoogle Scholar
  2. 2.
    Gallagher JC, Riggs BL, Eisman J, et al. Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients: effect of age and dietary calcium. J Clin Invest 1979; 64: 729–734.CrossRefPubMedGoogle Scholar
  3. 3.
    Cummings SR, Kelsey JL, Nevitt MC, O’Dowd KJ. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev 1985; 7: 178–208.PubMedGoogle Scholar
  4. 4.
    Jensen GF, Christiansen C, Boesen J, et al. Epidemiology of postmenopausal spinal and long bone fractures: a unifying approach to postmenopausal osteoporosis. Clin Orthop 1966; 45: 31–36.Google Scholar
  5. 5.
    Owen RA, Melton LJ, Johnson KA, et al. Incidence of Colle’s fracture in a North American community. Am J Public Health 1982; 72: 604–607.CrossRefGoogle Scholar
  6. 6.
    Gallagher JC, Melton LJ, Riggs BL. Epidemiology of fractures of the proximal femur in Rochester, Minnesota. Clin Orthop 1980; 150: 163–171.PubMedGoogle Scholar
  7. 7.
    Melton LJ, Ilstrup M, Riggs B, et al. Fifty year trend in hip fracture incidence. Clin Orthop 1982; 62: 144–149.Google Scholar
  8. 8.
    Wallace W. The increasing incidence of fractures of the proximal femur: an orthopedic epidemic. Lancet 1983; 2: 1413–14.CrossRefGoogle Scholar
  9. 9.
    Riggs BL, Melton LJ. Evidence for two distinct syndromes of involutional osteoporosis. Am J Med 1983; 75: 899–901.CrossRefPubMedGoogle Scholar
  10. 10.
    Eriksen EF, Colvard DS, Berg NJ, et al. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 1988; 241: 84–86.CrossRefPubMedGoogle Scholar
  11. 11.
    Komm BS, Terpening CM, Benz DJ, et al. Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteocarcoma cells. Science 1988241: 81–84.Google Scholar
  12. 12.
    Cummings SR. Epidemiology of osteoporotic fractures: selected topics. In Roche AF, ed. Osteoporosis: Current Concepts-Report of the 7th Ross Conference on Medical Research. Columbus, Ohio: Ross Laboratories; 1987: 3–8Google Scholar
  13. 13.
    Williams AR, Weiss NS, Ure Cl, et al. Effect of weight, smoking, and estrogen use on the risk of hip and forearm fractures in post-menopausal women. Obstet Gynecol 1982; 60: 695–699PubMedGoogle Scholar
  14. 14.
    Heaney RP, Gallagher JC, Johnston CC, et al. Calciumnutrition and bone health in the elderly. Am J Clin Nutr 1982; 36: 986–1013.PubMedGoogle Scholar
  15. 15.
    Hull RD, Raskob GE, Hirsh J. Prophylaxis of venous thrombembolism: an overview. Chest 1986(suppl); 89: 374S - 383S.Google Scholar
  16. 16.
    Riggs BL, Wahner HW. Bone densitometry and clinical decision-making in osteoporosis. Ann Intern Med 1988; 108: 293–295.PubMedGoogle Scholar
  17. 17.
    Cummings SR, Black D. Should perimenopausal women be screened for osteoporosis? Ann Intern Med 1986; 104: 817–823.PubMedGoogle Scholar
  18. 18.
    Lindsay R. Osteoporosis. Clin Geriatr Med 1988; 4: 411 430.Google Scholar
  19. 19.
    Bohr H, Schaadt O. Bone mineral content of the femoral bone and the lumbar spine measured in women with frac ture of the femoral neck by dual photon absorptiometry. Clin Orthop 1983; 1979: 240–245.Google Scholar
  20. 20.
    Pacifici R, Susman N, Carr PL, et al. Single and dual energy tomographic analysis of spinal trabecular bone: a comparative study in normal and osteoporotic women. J Clin Endocrinol Metab 1987; 64: 209–214.CrossRefPubMedGoogle Scholar
  21. 21.
    Cummings SR. Bone mineral densitometry (position paper, Health and Public Policy Committee, American Col lege of Physicians.) Ann Intern Med 1987; 107: 932–936.Google Scholar
  22. 22.
    Cameron JR, Mazess RB, Sorenson JA. Precision and accuracy of bone mineral determination by direct photon absorptiometry. Invest Radiol 1968; 3: 141–150.CrossRefPubMedGoogle Scholar
  23. 23.
    Silverberg S, Shane E, delaCruz L, et al. Skeletal disease in primary hyperparathyroidism. J Bone Miner Res 1988;3(suppl 1):89. Abstract.Google Scholar
  24. 24.
    Riggs BL, Wahner HW, Dunn WL, et al. Differential changes in bone mineral density of the appendicular and axial skeleton with aging. J Clin Invest 1981; 67: 328–335.CrossRefPubMedGoogle Scholar
  25. 25.
    Wahner WH, Riggs BL. Methods and application of bone densitometry in clinical diagnosis. CRC Crit Rev Clin Lab Sci 1986; 24: 217–233.CrossRefGoogle Scholar
  26. 26.
    Cann CE. Quantitative computed tomography for bone mineral analysis: technical considerations. In: Genant HK, ed. Osteoporosis Update. San Francisco, Califor- nia: Radiology Research and Educational Foundation; 1987:131–144.Google Scholar
  27. 27.
    Matkovic V, Kostial K, Simonovic I, et al. Bone status and fracture rates in two regions of Yugoslavia. Am J Clin Nutr 1979; 32: 540–548.PubMedGoogle Scholar
  28. 28.
    Heaney RP. Calcium, bone health and osteoporosis. Bone Miner Res 1986; 4: 255–301.Google Scholar
  29. 29.
    Finn Jensen G, Christiansen C, Transbol I. Treatment of postmenopausal osteoporosis: a controlled therapeutic; trial comparing o estrogen/gestagen, 1,25 dihydroxy vitamin D3 and calcium. Clin Endocrinol 1982; 16: 515–524.CrossRefGoogle Scholar
  30. 30.
    Heaney RP, Recker RR, Saville PD. Calcium balance and calcium requirements in middle-aged women. Am J Cin Nutr 1977; 30: 1603–1611.Google Scholar
  31. 31.
    Dalsky GP, Stocke KS, Ehsani AA, et al. Weight bearing. exercise training and lumbar bone mineral content in post menopausal women. Ann Intern Med 1988;108:824–828.Google Scholar
  32. 32.
    Drinkwater BD, Nilson KC, Chestnut CH. Bone mineral content of amenorrheic and eumenorrheic athletes. N Engl J Med 1984; 311: 277–281.CrossRefPubMedGoogle Scholar
  33. 33.
    Heaney RP, Recker RR, Saville PD. Menopausal changes in bone remodeling. J Lab Clin Med 1978; 92: 964–970.PubMedGoogle Scholar
  34. 34.
    Nachtigall LE, Nachtigall RH, Nachtigall RD. Estrogen replacement therapy, I: a 10 year prospective study in the relationship of osteoporosis. Obstet Gynecol 1979; 53: 277–284.PubMedGoogle Scholar
  35. 35.
    Lindsay R, Hart DM, MacLean A, et al. Bone response to termination of oestrogen treatment. Lancet 1978; 1: 1325–1327.CrossRefPubMedGoogle Scholar
  36. 36.
    Marcus R, Cann C, Madvig P, et al. Menstrual function and bone mass in elite women distance runners. Ann Intern Med 1985; 102: 158–163.Google Scholar
  37. 37.
    Ettinger B, Genant HK, Cann CE. Long term estrogen therapy prevents bone loss and fracture. Ann Intern Med 1985; 102: 319–324.PubMedGoogle Scholar
  38. 38.
    Hutchinson TA, Polansky JM, Feinstein AR. Postmenopausal oestrogens protect against fracture of the hip and distal radius. Lancet 1979; 2: 705–709.CrossRefPubMedGoogle Scholar
  39. 39.
    Kreiger N, Kelsey JL, Holford TR. An epidemiological study of hip fracture in postmenopausal women. Am J Epidemiol 1982; 116: 141–148.PubMedGoogle Scholar
  40. 40.
    Smith DM, Khairi MRA, Johnston CC. The loss of bone mineral with aging and its relationship to risk of fracture. J Clin Invest 1975; 56: 311–318.CrossRefPubMedGoogle Scholar
  41. 41.
    Bush TL, Barrett-Connor E. Noncontraceptive estrogen use and cardiovascular disease. Epidemiol Rev 1985; 7: 80–104.Google Scholar
  42. 42.
    Stampfer MJ, Willett WC, Colditz GA. A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med 1985; 313: 1044–1049.CrossRefPubMedGoogle Scholar
  43. 43.
    Wilson PWF, Garrison RJ, Castelli WP. Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50: the Framingham study. NEngl J Med 1985; 313: 1038–1043.CrossRefGoogle Scholar
  44. 44.
    Shapiro S, Kelley JP, Rosenberg L. Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens. N Engl J Med 1985; 313: 969–972.CrossRefPubMedGoogle Scholar
  45. 45.
    Horowitz RI, Feinstein AR. Alternative analytic methods for case control studies of estrogens and endometrial N Engl J Med 1978; 299: 1088–1094.CrossRefGoogle Scholar
  46. 46.
    Chu J, Schweed AI, Weiss NS. Survival among women with endometrial cancer: a comparison of estrogen users and non users. Am J Obstet Gynecol 1982; 143: 569–573.PubMedGoogle Scholar
  47. 47.
    Gambrell RD, Massey FM, Castaneda TA, et al. Reduced incidence of endometrial cancer among postmenopausal women treated with progestogens. J Am Geriatr Soc 1979; 27: 389–394.PubMedGoogle Scholar
  48. 48.
    Gambrell RD. The menopause: benefits and risks of estrogen-progestogen replacement therapy. Fertil Steril 1982; 37: 457–477.PubMedGoogle Scholar
  49. 49.
    Wingo PA, Layde PM, Lee NC, et al. The risk of breast cancer in postmenopausal women who have used estrogen replacement therapy. JAMA 1987; 257: 209–215.CrossRefPubMedGoogle Scholar
  50. 50.
    Horowitz RI, Feinstein AR. Effect of clinical features on the association of estrogens and breast cancer. Am J Med 1984; 76: 192–198.CrossRefGoogle Scholar
  51. 51.
    Hoover R, Glass A, Finkle WG, et al. Conjugated estrogens and breast cancer risk in women. JNCI 1981; 67: 815–820.PubMedGoogle Scholar
  52. 52.
    Kelsey JL, Fischer DB, Holford TR, et al. Exogenous estrogens and other factors in the epidemiology of breast cancer. JNCI 1981; 67: 327–333.PubMedGoogle Scholar
  53. 53.
    Ettinger B, Genant HK, Cann CE. Long term estrogen therapy prevents bone loss and fracture. Ann Intern Med 1985; 102: 319–324.PubMedGoogle Scholar
  54. 54.
    McDermott MT, Kidd GS. The role of calcitonin in the development and treatment of osteoporosis. Endocr Rev 1987; 8: 377–390.CrossRefPubMedGoogle Scholar
  55. 55.
    Gruber HE, Ivey JL, Baylink DL, et al. Long term calcitonin therapy in postmenopausal osteoporosis. Metabolism 1984; 33: 295–303.CrossRefPubMedGoogle Scholar
  56. 56.
    Mazzuoli GF, Passeri M, Gennari C, et al. Effects of salmon calcitonin in postmenopausal osteoporosis: a controlled double-blind clinical study. Calcif Tissue Int 1986; 38: 3–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Riggs BL, Seeman E, Hodgson SF, et al. Effect of the fluoride/calcium regimen on vertebral fracture occurence in postmenopausal osteoporosis. N Engl J Med 1982; 306: 446–450.CrossRefPubMedGoogle Scholar
  58. 58.
    Inkovaana J, Heikinheimo R, Jarvinen K, et al. Prophylactic fluoride treatment and aged bones. Br Med J 1975; 3: 73–74.CrossRefGoogle Scholar
  59. 59.
    Einhorn TA, Vigorita VJ. Unique histology of the fracture callus in a sodium fluoride-treated osteoporotic patient with hip fracture. In: Christiansen C, ed. Osteoporosis 1987. Copenhagen, Denmark: Osteopress ApS; 1987: 262–265.Google Scholar
  60. 60.
    Gutteridge DH, Price RJ, Nicholson GC, et al. Fluoride in osteoporotic fractures-trabecular increase, vertebral protection, femoral fractures. In: Christiansen C, et al, eds. Osteoporosis 2. Copenhagen International Symposium Osteo, June 1984.Google Scholar
  61. 61.
    O’Duffy JD, Wahner HW, O’Fallon WM, et al. Mechanism of acute lower extremity pain syndrome in fluoride-treated osteoporotic patients. Am J Med 1986; 80: 56 1566.Google Scholar
  62. 62.
    Baylink DJ, Ivey JL. Sodium fluoride for osteoporosis: some unanswered questions. JAMA 1980; 245: 463–464.CrossRefGoogle Scholar
  63. 63.
    Wasnich RD, Benfante RJ, Yano K, et al. Thiazide effect on the mineral content of bone. N Engl J Med 1983; 309: 344–347.CrossRefPubMedGoogle Scholar
  64. 64.
    Transbol I, Christensen GF, Jensen GF, et al. Thiazide for the postponement of postmenopausal bone loss. Metabolism 1982; 31: 383–386.CrossRefPubMedGoogle Scholar
  65. 65.
    Christiansen C, Christensen MS, Hagen C, et al. Effects of natural estrogen-gestagen and thiazide on coronary risk factors in normal postmenopausal women. Acta Ob-stet Gynecol Scand 1981; 60: 407–412.CrossRefGoogle Scholar
  66. 66.
    Multiple Risk Factor Intervention Trial Research Group. Multiple risk factor intervention trial: risk factor changes and mortality results. JAMA 1982; 248: 1465–1477.CrossRefGoogle Scholar
  67. 67.
    Chestnut CH, Ivey JL, Gruber HE, et al. Stanozolol in postmenopausal osteoporosis: therapeutic efficacy and possible mechanisms of action. Metabolism 1983; 32: 57 1580.Google Scholar
  68. 68.
    Slovik DM, Rosenthal D, Doppelt SH, et al. Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1–34) and 1,25 dihydroxyvitamin D. Bone Miner Res 1986; 1: 377–381.CrossRefGoogle Scholar
  69. 69.
    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: 372–374.CrossRefPubMedGoogle Scholar
  70. 70.
    Jensen GF, Meinecke B, Boesen J, et al. Does 1,25(OH)2D3 accelerate spinal bone loss? Clin Orthop 1985; 192: 215–221.PubMedGoogle Scholar
  71. 71.
    Frost HM. `Coherence’ treatment of osteoporosis by ADFR scheme. In: DeLuca HF, Frost HM, Lee WS, et al, eds. Osteoporosis: Recent Advances in Pathogenesis and Treatment. Baltimore, Md, University Park Press; 1981: 393–396.Google Scholar
  72. 72.
    Hahn TJ, Halstead LR, Teitelbaum SL, et al. Altered mineral metabolism in glucocorticoid-induced osteopenia: effect of 25-hydroxyvitamin D. J Clin Invest 1979; 64: 655–665.CrossRefPubMedGoogle Scholar
  73. 73.
    Reid IR, Ibbertson HK. Calcium supplements in the prevention of steroid-induced osteoporosis. Am J Clin Nutr 1986; 44: 287–290.PubMedGoogle Scholar
  74. 74.
    Seeman E, Melton LJ, O’Fallon WM, et al. Risk factors for spinal osteoporosis in men. Am J Med 1983; 75: 977983.Google Scholar
  75. 75.
    Frame B, Parfitt AM. Osteomalacia: current concepts Ann Intern Med 1978; 89: 996–982.Google Scholar
  76. 76.
    Holick MF. Vitamin D requirements for the elderly. Clin Nutr 1986; 5: 121–129.Google Scholar
  77. 77.
    Parfitt AM, Frame B. Treatment of rickets and osteomalacia. Semin Drug Treat 1972; 2: 83–115.PubMedGoogle Scholar
  78. 78.
    Heath H, Hodgson SF, Kennedy MA. Primary hyperparathyroidism: incidence, morbidity and potential economic impact in a community. N Engl J Med 1980; 302: 189–193.CrossRefPubMedGoogle Scholar
  79. 79.
    Mallette LE. Primary hyperparathyroidism: clinical and biochemical features. Medicine 1974; 53: 127–146.CrossRefPubMedGoogle Scholar
  80. 80.
    Karpati G, Frame B. Neuropsychiatric disorders in primary hyperparathyroidism. Arch Neurol 1964; 10: 387397.Google Scholar
  81. 81.
    Bilezikian JP. The medical management of primary hyperparathyroidism. Ann Intern Med 1982; 96: 198–202.PubMedGoogle Scholar
  82. 82.
    Marcus R, Madvig P, Crim M, et al. Congugated estrogens in the treatment of postmenopausal women with hyperparathyroidism. Ann Intern Med 1984; 100: 633–640.PubMedGoogle Scholar
  83. 83.
    Selby PL, Peacock M. Ethinyl estradiol and norethin drone in the treatment of primary hyperparathyroidism in postmenopausal women. N Engl J Med 1986; 314: 1481–1485.CrossRefPubMedGoogle Scholar
  84. 84.
    Scholz DA, Purnell DC. Asymptomatic primary hyper parathyroidism: 10 year prospective study. Mayo Clin Proc 1981; 56: 473–478.PubMedGoogle Scholar
  85. 85.
    Singer FR. Paget’s Disease of Bone. New York, NY: Plenum Medical Book Co; 1977.Google Scholar
  86. 86.
    Frame B. Paget disease: a review of current knowledge. Radiology 1981;141:21–24.Google Scholar
  87. 87.
    Singer FR. Paget’s disease of bone. In: Martin TJ, Raisz LG, eds. Clinical Endocrinology of Calcium Metabolism. New York, NY: Marcel Dekker Inc; 1987: 369–402.Google Scholar
  88. 88.
    Singer FR, Fredericks RS, Minkin C. Salmon calcitonin therapy for Paget’s disease of bone: the problem of acquired clinical resistance. Arthritis Rheum 1980; 23: 1148–1154.CrossRefPubMedGoogle Scholar
  89. 89.
    Fleisch H. Biphosphonates: mechanisms of action and clinical applications. In: Peck WA, ed. Bone and Mineral Research Annual 1. Amsterdam, the Netherlands: Excerpta Medica; 1983: 319–357.Google Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Diane Meier

There are no affiliations available

Personalised recommendations