The Relationship of Peak Bone Mass, Aging, and Bone Loss to Osteoporosis and Fragility Fractures

  • Joseph BorrelliJr.


Generally, peak bone mass is reached during early adulthood, and there are numerous factors that can negatively affect its attainment. These factors include genetics, nutrition, exercise, and the use of certain medications. During and after peak bone mass is obtained, basic multicellular units are instrumental in skeletal homeostasis and maintaining healthy bone. Unfortunately, as we age, this homeostasis between bone resorption and bone formation is tilted toward resorption, often leading to the development of poor bone quality that, when severe, is referred to as osteoporosis. The world’s population is growing older, leading to an increasing incidence of people with poor bone quality and potentially osteoporosis. Fractures are more likely to occur in weakened bone, and commonly these fractures occur as a result of low-energy trauma such as a fall from a standing height. Fractures involving osteoporotic bone are often comminuted, difficult to securely repair, and slow to heal. Individuals who sustain fractures as a result of low-energy trauma in the setting of skeletal fragility often also have osteoarthritis, generalized muscle weakness, and cardiovascular conditions, which make it difficult for them to ambulate and protect injured extremities during healing. Additionally, these older patients typically have a shorter life expectancy than that of younger trauma patients. Each of these factors makes joint arthroplasty a more attractive and more predictable treatment option than conventional open reduction and internal fixation (ORIF). This chapter outlines the factors which influence the attainment of peak bone mass and maintenance of normal bone as well as the primary age-related causes of poor bone quality/osteoporosis and reviews the tsunami of fragility fractures that is expected worldwide as the world’s population continues to grow older.


Osteoporosis Fragility fracture Aging Peak bone mass Genetics Lifestyle Chronic disease Bone homeostasis Bone remodeling Basic multinucleated units Senescence Hormonal changes Joint arthroplasty Malunion Nonunion Delayed bone healing 


  1. 1.
    Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA, et al. Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab. 2011;96:3160–9.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Cooper C, Westlake S, Harvey N, Javaid K, Dennison E, Hanson M. Review: developmental origins of osteoporotic fractures. Osteoporos Int. 2006;17(3):337–47.CrossRefPubMedGoogle Scholar
  3. 3.
    Hendrickx G, Boudin E, Van Hul W. A look behind the scenes: the risk and pathogenesis of primary osteoporosis. Nat Rev Rheumatol. 2015;11:462–74.CrossRefPubMedGoogle Scholar
  4. 4.
    Balasuriya, et al. Peak bone mass and bone microarchitecture in adults born with low birth weight preterm or a term: a cohort study. J Clin Endocrinol Metab. 2017;102(7):2491–500. Scholar
  5. 5.
    Looker AC, Borrud LG, Hughes JP, Fan B, Shepherd JA, Melton L Jr. Lumbar spine and proximal femur bone mineral density, bone mineral content, and bone area: United States, 2005–2008. Vital Health Stat. 2012;11:1–132.Google Scholar
  6. 6.
    Kelly T, Wilson KE, Heymsfield SB. Dual energy xray absorptiometry body composition reference values from NHANES. PLoS One. 2009;4:e7038.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Kindblom JM, Lorentzon M, Norjavarra E, Hellqvist A, Nilsson S, Mellstrom D, et al. Pubertal timing predicts previous fractures and BMD in young adult men: the GOOD study. J Bone Miner Res. 2006;21:790–5.CrossRefPubMedGoogle Scholar
  8. 8.
    Krall EA, Dawson-Hughes B. Heritable and lift-style determinants of bone mineral density. J Miner Res. 1993;8:1–9.Google Scholar
  9. 9.
    Seeman EE, Hopper JL, Bach LA, Cooper ME, Parkinson E, McKay J, et al. Reduced bone mass in daughters of women with osteoporosis. N Engl J Med. 1989;320:554–8.CrossRefGoogle Scholar
  10. 10.
    Warrington NM, Kemp JP, Tilling K, Tobias JH, Evans DM. Genetic variants in adult bone mineral density acquisition in adolescence. Hum Mol Genet. 2015;24:4158–66.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mitchell JA, Chesi A, Elci O, McCormack SE, Roy SM, Kalkwarf HJ, Lappe JM, Gilsanz V, Oberfield SE, Shepherd JA, Kelly A, Grant SF, Zemel BS. Genetic risk scores implicated in adult bone fragility associate with pediatric bone density. J Bone Miner Res. 2016;31(4):789–95. Scholar
  12. 12.
    Braun M, Palacios C, Wigertz K, Jackman LA, Bryant RJ, McCabe LD, Martin BR, McCabe GP, Peacock M, Weaver CM. Racial differences in skeletal calcium retention in adolescent girls on a range of controlled calcium intakes. Am J Clin Nutr. 2007;85:1657–63.CrossRefGoogle Scholar
  13. 13.
    Anderson LN, Heong SW, Chen Y, Thorpe KE, Adeli K, Howard A, Sochett E, Birken CS, Parkin PC, Maguire JL. Vitamin D and fracture risk in early childhood: a case-control study. Am J Epidemiol. 2017;185:1255–62.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest. 1998;102:274–82.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, et al. Glucocorticoids and the osteoclast. Ann N Y Acad Sci. 2007;1116:335–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Bonjour J-P, Ammann P, Chevalley T, Ferrari S, Rizzoli R. Nutritional aspects of bone growth: an overview. In: New SA, Bonjour J-P, editors. Nutritional aspects of bone health. Cambridge UK: The Royal Society of Chemistry; 2005. p. 111–27.Google Scholar
  17. 17.
    Tveit M, Rosengren BE, Nilsson JA, Karisson MK. Exercise in youth: high bone mass, large bone size, and low fracture risk in old age. Scand J Med Sci Sports. 2015;25(4):453–61. Scholar
  18. 18.
    Nilsson M, Ohlsson C, Mellstrom D, Lorentzon M. Previous sport activity during childhood and adolescence is associated with increased cortical bone size in young adult men. J Bone Miner Res. 2009;24:125–33.CrossRefPubMedGoogle Scholar
  19. 19.
    Detter FT, Rosengren BE, Dencker M, Nilsson JA, Karlsson MK. A 5-year exercise program in pre- and peripubertal children improves bone mass and bone size without affecting fracture risk. Calcif Tissue Int. 2013;92(4):385–93. Scholar
  20. 20.
    Semeao EJ, Stallings VA, Peck SN, Piccoli DA. Vertebral compression fractures in pediatric patients with Crohn’s disease. Gastroenterology. 1997;112:1710–3.CrossRefPubMedGoogle Scholar
  21. 21.
    Lentle B, Ma J, Jaremko JL, Siminoski K, Matzinger MA, Shenouda N, et al. The radiology of vertebral fractures in childhood osteoporosis related to glucocorticoid administration. J Clin Densitom. 2016;19:81–8.CrossRefPubMedGoogle Scholar
  22. 22.
    LeBlanc CM, Ma J, Talijaard M, Roth J, Scuccimarri R, Miettunen P, et al. Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. J Bone Miner Res. 2015;30:1667–75.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Cummings EA, Ma J, Fernandez C, Halton J, Alos N, Miettunen PM, et al. Incident vertebral fractures in children with leukemia during the four years following diagnosis. J Clin Endocrinol Metab. 2015;100:3408–17.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Weber DR, Haynes K, Leonard MB, Willi SM, Denburg MR. Type 1 diabetes is associated with an increased risk of fracture across the life span: a population based cohort study using The Health Improvement Network (THIN). Diabetes Care. 2015;38:1913–20.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Burnham JM, Shults J, Weinstein R, Lewis JD, Leonard MB. Childhood onset arthritis is associated with an increased risk of fracture: a population based study using the General Practice Research Database. Ann Rheum Dis. 2006;65:1074–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Canalis E, Delany AM. Mechanisms of glucocorticoid action in bone. Ann N Y Acad Sci. 2002;966:73–81.CrossRefPubMedGoogle Scholar
  27. 27.
    Schakman O, Kalista S, Barbé C, Loumaye A, Thissen JP. Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol. 2013;45(10):2163–72.CrossRefPubMedGoogle Scholar
  28. 28.
    Deakin BY, et al. Wheater’s functional histology : a text and colour atlas. 5th ed. Edinburgh: Churchill Livingstone/Elsevier; 2006. p. 189–90.Google Scholar
  29. 29.
    Hall AC, Guyton JE. Textbook of medical physiology. 11th ed. Philadelphia: W.B. Saunders; 2005. p. 981.Google Scholar
  30. 30.
    Weiner S, Wagner HD. Ann Rev Mater Sci. 1998;28:271. Scholar
  31. 31.
    Tortora GJ. Principles of human anatomy. New York: Wiley; 2002.Google Scholar
  32. 32.
    Hu F, Jiang C, Tang P, Wang Y. Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis. Injury. 2012;43(6):676–85. Scholar
  33. 33.
    Smith T, Pelpola K, Ball M, Ong A, Myint PK. Pre-operative indicators for mortality following hip fracture surgery: a systematic review and meta-analysis. Age Aging. 2014;43(4):464–71. Scholar
  34. 34.
    Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB. Incidence and mortality of hip fractures in the United States. JAMA. 2009 Oct14;302(14):1573–9. Scholar
  35. 35.
    Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, Licata A, Benhamou L, Geusens P, Flowers K, Stracke H, Seeman E. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001;285(3):320–3.CrossRefPubMedGoogle Scholar
  36. 36.
    Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R. National Osteoporosis Foundation. Osteoporos Int. 2014;25(10):2359–81.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Abrahamyan MG. On the physics of the bone fracture. Inter J Clin Exper Sci. 2017;3(6):74–7. Scholar
  38. 38.
    Turner CH, Wang T, Burr DB. Shear strength and fatigue properties of human cortical bone determined from pure shear tests. Calcif Tissue Int. 2001;69(6):373–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Bankoff ADP. Biomechanical characteristics of the bone. In: Goswami T, editor. Human musculoskeletal biomechanics. London: Intech Open Limited; 2012. p. 61–89.Google Scholar
  40. 40.
    Holtrop ME. The ultrastructure of bone. Ann Clin Lab Sci. 1975;5(4):264–71.PubMedGoogle Scholar
  41. 41.
    Ritchie RO. How does human bone resist-fracture? Ann NY Acad Sci. 2010;1192:72–80.CrossRefPubMedGoogle Scholar
  42. 42.
    Kanis JA, Oden A, Johnell O, Jonsson B, de Laet C, Dawson A. The burden of osteoporosis fractures: a method for setting intervention thresholds. Osteoporos Int. 2001;12(5):417–27.CrossRefPubMedGoogle Scholar
  43. 43.
    Parfitt AM, Mundy GR, Roodman GD, Hughes DE, Boyce BF. A new model of the regulation of bone resorption, with particular reference to the effects of bisphosphonates. J Bone Miner Res. 1996;11:150–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Frost HM. Bone remodeling and its relationship to metabolic bone disease. Springfield: Charles Thompson; 1973.Google Scholar
  45. 45.
    Triffitt JT. The stem cell of the osteoblast. In: Bilezikian JP, Raisz LG, Rodan GA, editors. Principles of bone biology. San Diego: Academic; 1996. p. 39–50.Google Scholar
  46. 46.
    Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of OP. Endocr Rev. 2000;21(2):115–37.PubMedGoogle Scholar
  47. 47.
    Parfitt AM. Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in the adult human bone. J Cell Biochem. 1994;55:273–86.CrossRefPubMedGoogle Scholar
  48. 48.
    Raggatt LJ, Partridge NC. J Biol Chem. 2010;285(33):25103–8.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Manolagas SC, Jilka RI. Bone marrow, cytokines, and bone remodeling- emerging insights into the pathophysiology of osteoporosis. N Engl J Med. 1995;332:305–11.CrossRefPubMedGoogle Scholar
  50. 50.
    Klein-Nulend J, Bakker AS. Mechanosensation and transduction in osteocytes. Bone. 2013;54:182–90.CrossRefPubMedGoogle Scholar
  51. 51.
    He W, Goodkind D, Kowal P, U.S. Census Bureau. International population reports, P95/16–1, An aging world: 2015. Washington, DC: U.S. Government Publishing Office; 2016.Google Scholar
  52. 52.
    Arias E. United States life tables, 2010, National Vital Statistics Reports 63/7. Hyattsville: National Center for Health Statistics; 2014.Google Scholar
  53. 53.
    Solomon DH, Finkelstein JS, Katz JN, Mogun H, Avorn J. Underuse of osteoporosis medication in elderly patients with fractures. Am J Med. 2003;115(5):98–400.CrossRefGoogle Scholar
  54. 54.
    Solomon DH, Joshston SS, Boytsov NN, McMorrow D, Lane JM, Krohn KD. Osteoporosis medication use after hip fractures in US patients between 2002–2011. J Bone Miner Res. 2014;29(9):1929–37.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Kassem M, Marie PJ. Senescence-associated intrinsic mechanisms of osteoblast dysfunction. Aging Cell. 2011;10:191–7.CrossRefPubMedGoogle Scholar
  56. 56.
    Jilka RL, Weinstein RS, Takahashi K, Parfitt AM, Manolagas SC. Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence. J Clin Invest. 1996;97:1732–40.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Kajkenova O, Lecka-Czernik B, Gubrij I, Hauser SP, Takahashi K, Parfitt AM, Jilka RL, Manolags SC, Lipschitz DA. Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6 murine model of defective osteoblastogenesis and low turnover osteopenia. J Bone Miner Res. 1997;12:1772–9.CrossRefPubMedGoogle Scholar
  58. 58.
    Parfitt AM. Bone-forming cells in clinical conditions. In: Hall BK, editor. Bone. The osteoblast and osteocyte, vol. 1. Boca Raton: Telford Press and CRC Press; 1990. p. 351–429.Google Scholar
  59. 59.
    Rozman C, Feliu E, Berga L, Reverter JC, Climent C, Ferran MJ. Age-related variations of fat tissue fraction in normal human bone marrow depend both on size and number of adipocytes: a stereological study. Exp Hematol. 1989;17:34–7.PubMedGoogle Scholar
  60. 60.
    Gimble JM, Robinson CE, Wu X, Kelley KA. The function of adipocytes in the bone marrow stroma: an update. Bone. 1996;19:421–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Tavassoli M. Fatty involution of marrow and the role of the hematopoietic microenvironment. Clifton: Humana Press; 1989. p. 157–87.Google Scholar
  62. 62.
    Kajkenova O, Gubrij I, Hauser SP, Takahashi K, Jilka RL, Manolagas SC, Lipshitz DA. Increased hematopoiesis accompanies reduced osteoblastogenesis in the senescence-accelerated mouse (SAM-P/6). J Bone Miner Res. 1995;10(Suppl 1):S431. AbstractGoogle Scholar
  63. 63.
    Manolagas SC. Cellular and molecular mechanisms of osteoporosis. Aging Clin Exp Res. 1998;10:182–90.CrossRefGoogle Scholar
  64. 64.
    Sundeep K, Merry JO, David GM. Estrogen and the skeleton. Trends Endocrinol Metab. 2012;23(11):576–81.CrossRefGoogle Scholar
  65. 65.
    Ucer S, Lyer S, Kim H, Han L, Rutlen C, Allison K, Thostenson JD, Cabo R, Jilka RL, O’Brien C, Almeida M, Manolaga SC. The effects of aging and sex steroid deficiency on the murine skeleton are independent and mechanistically distinct. J Bone Miner Res. 2017;32(3):560–74.CrossRefPubMedGoogle Scholar
  66. 66.
    Goldstein SA, Goulet Z, McCubbrey D. Measurement and significance of three-dimensional architecture integrity of trabecular bone. Calcif Tissue Int. 1993;53(Suppl 1):127–33.CrossRefGoogle Scholar
  67. 67.
    Seeman E, Bianchi G, ADami S, et al. Osteoporosis in men: consensus is premature. Calcif Tissue Int. 2004;75:120–2.CrossRefPubMedGoogle Scholar
  68. 68.
    Seebeck J, Goldhahn J, Morlock MM, Schneider E. Mechanical behavior of screws in normal and osteoporotic bone. Osteoporos Int. 2005;16(Suppl 2):107–11.CrossRefGoogle Scholar
  69. 69.
    Chammout GK, Mukka SS, Carlsson T, Neander GF, Stark AW, Skoldenberg OG. Total hip replacement versus open reduction and internal fixation of displaced femoral neck fractures: a randomized long-term follow-up study. J Bone Joint Surg. 2012;94(21):1921–8.CrossRefPubMedGoogle Scholar
  70. 70.
    Blomfeldt R, Tornkvist H, Ponzer S, Soderqvist A, Tidermark J. Comparison of internal fixation with total hip replacement for displaced femoral neck fractures. Randomized, controlled trial performed at four years. J Bone Joint Surg Am. 2005;87(8):1680–8.PubMedGoogle Scholar
  71. 71.
    Grubhofer F, Wieser K, Meyer DC, Catanzaro S, Beeler S, Riede U, Gerber C. Reverese total shoulder arthroplasty for acute head-splitting, 3- and 4-part fractures of the proximal humerus in the elderly. J Shoulder Elb Surg. 2016;25(10):1690–8.CrossRefGoogle Scholar
  72. 72.
    Rajaee SS, Yalamanchili D, Noori N, Debbi E, Mirocha J, Lin CA, Moon CN. Increasing use of reverse total shoulder arthroplasty for proximal humerus fractures in elderly patients. Orthopedics. 2017;40(6):e982–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Joseph BorrelliJr.
    • 1
  1. 1.BayCare Medical GroupLutzUSA

Personalised recommendations