Skip to main content

Advertisement

SpringerLink
Log in

Osteoporosis in young adults: pathophysiology, diagnosis, and management

  • Review
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Postmenopausal osteoporosis is mainly caused by increased bone remodeling resulting from estrogen deficiency. Indications for treatment are based on low areal bone mineral density (aBMD, T-score ≤ −2.5), typical fragility fractures (spine or hip), and more recently, an elevated 10-year fracture probability (by FRAX®). In contrast, there is no clear definition of osteoporosis nor intervention thresholds in younger individuals. Low aBMD in a young adult may reflect a physiologically low peak bone mass, such as in lean but otherwise healthy persons, whereas fractures commonly occur with high-impact trauma, i.e., without bone fragility. Furthermore, low aBMD associated with vitamin D deficiency may be highly prevalent in some regions of the world. Nevertheless, true osteoporosis in the young can occur, which we define as a T-score below −2.5 at spine or hip in association with a chronic disease known to affect bone metabolism. In the absence of secondary causes, the presence of fragility fractures, such as in vertebrae, may point towards genetic or idiopathic osteoporosis. In turn, treatment of the underlying condition may improve bone mass as well. In rare cases, a bone-specific treatment may be indicated, although evidence is scarce for a true benefit on fracture risk. The International Osteoporosis Foundation (IOF) convened a working group to review pathophysiology, diagnosis, and management of osteoporosis in the young, excluding children and adolescents, and provide a screening strategy including laboratory exams for a systematic approach of this condition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. Constitutional thinness (CT), or Leanness, was identified over the last decades as a nonpathological state of underweight that does not meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria of anorexia nervosa. Contrary to the later pathology, the nonpathological state of CT in adult women is supported by the presence of menstruations, normal thyroid and cardiac functions, and normal insulin sensitivity. Moreover, CT individuals are characterized by a body weight that has always been in the lower percentiles for age, gender, and ethnicity. Familiality and heritability of thinness were also described or demonstrated. For further reading, see [52–54].

References

  1. (1991) Diagnosis, prophylaxis and treatment of osteoporosis. In American Journal of Medicine. Consensus development conference, 90, pp 170–210

  2. (1994) World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Technical report series. In. Geneva

  3. Seeman E, Bianchi G, Khosla S, Kanis JA, Orwoll E (2006) Bone fragility in men—where are we? Osteoporos Int 17:1577–1583

    Article  PubMed  CAS  Google Scholar 

  4. Kanis JA, Oden A, Johnell O et al (2007) The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 18:1033–1046

    Article  PubMed  CAS  Google Scholar 

  5. Compston J, Cooper A, Cooper C, Francis R, Kanis JA, Marsh D, McCloskey EV, Reid DM, Selby P, Wilkins M (2009) Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. Maturitas 62:105–108

    Article  PubMed  CAS  Google Scholar 

  6. Dawson-Hughes B, Tosteson AN, Melton LJ 3rd, Baim S, Favus MJ, Khosla S, Lindsay RL (2008) Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int 19:449–458

    Article  PubMed  CAS  Google Scholar 

  7. Kanis JA, Burlet N, Cooper C, Delmas PD, Reginster JY, Borgstrom F, Rizzoli R (2008) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 19:399–428

    Article  PubMed  CAS  Google Scholar 

  8. Bianchi ML (2007) Osteoporosis in children and adolescents. Bone 41:486–495

    Article  PubMed  Google Scholar 

  9. Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Lewiecki EM, Silverman S (2008) Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Position Development Conference. J Clin Densitom 11:75–91

    Article  PubMed  Google Scholar 

  10. Bonjour JP, Chevalley T, Rizzoli R, Ferrari S (2007) Gene–environment interactions in the skeletal response to nutrition and exercise during growth. Med Sport Sci 51:64–80

    Article  PubMed  Google Scholar 

  11. Chevalley T, Rizzoli R, Hans D, Ferrari S, Bonjour JP (2005) Interaction between calcium intake and menarcheal age on bone mass gain: an eight-year follow-up study from prepuberty to postmenarche. J Clin Endocrinol Metab 90:44–51

    Article  PubMed  CAS  Google Scholar 

  12. Ferrari S, Rizzoli R, Slosman D, Bonjour JP (1998) Familial resemblance for bone mineral mass is expressed before puberty. J Clin Endocrinol Metab 83:358–361

    Article  PubMed  CAS  Google Scholar 

  13. Bailey DA, Wedge JH, McCulloch RG, Martin AD, Bernhardson SC (1989) Epidemiology of fractures of the distal end of the radius in children as associated with growth. J Bone Joint Surg Am 71:1225–1231

    PubMed  CAS  Google Scholar 

  14. Clark EM, Ness AR, Bishop NJ, Tobias JH (2006) Association between bone mass and fractures in children: a prospective cohort study. J Bone Miner Res 21:1489–1495

    Article  PubMed  Google Scholar 

  15. Ferrari SL, Chevalley T, Bonjour JP, Rizzoli R (2006) Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility? J Bone Miner Res 21:501–507

    Article  PubMed  Google Scholar 

  16. Khosla S, Melton LJ 3rd, Dekutoski MB, Achenbach SJ, Oberg AL, Riggs BL (2003) Incidence of childhood distal forearm fractures over 30 years: a population-based study. JAMA 290:1479–1485

    Article  PubMed  CAS  Google Scholar 

  17. Boyce AM, Gafni RI (2011) Approach to the child with fractures. J Clin Endocrinol Metab 96:1943–1952

    Article  PubMed  CAS  Google Scholar 

  18. Ferrari S (2006) Single gene mutations and variations affecting bone turnover and strength. BoneKey 3:11–29

    Article  Google Scholar 

  19. Rizzoli R, Bianchi ML, Garabedian M, McKay HA, Moreno LA (2010) Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly. Bone 46:294–305

    Article  PubMed  Google Scholar 

  20. Rauch F, Travers R, Glorieux FH (2006) Cellular activity on the seven surfaces of iliac bone: a histomorphometric study in children and adolescents. J Bone Miner Res 21:513–519

    Article  PubMed  Google Scholar 

  21. Seeman E (2002) Pathogenesis of bone fragility in women and men. Lancet 359:1841–1850

    Article  PubMed  Google Scholar 

  22. Nordstrom P, Neovius M, Nordstrom A (2007) Early and rapid bone mineral density loss of the proximal femur in men. J Clin Endocrinol Metab 92:1902–1908

    Article  PubMed  CAS  Google Scholar 

  23. Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McDaniel L, Amin S, Rouleau PA, Khosla S (2008) A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res 23:205–214

    Article  PubMed  Google Scholar 

  24. Riggs BL, Wahner HW, Melton LJ 3rd, Richelson LS, Judd HL, Offord KP (1986) Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause. J Clin Invest 77:1487–1491

    Article  PubMed  CAS  Google Scholar 

  25. Ferrari S (2008) Human genetics of osteoporosis. Best Pract Res Clin Endocrinol Metab 22:723–735

    Article  PubMed  CAS  Google Scholar 

  26. Karasik D, Ferrari SL (2008) Contribution of gender-specific genetic factors to osteoporosis risk. Ann Hum Genet 72:696–714

    Article  PubMed  CAS  Google Scholar 

  27. Sylvester FA (2005) IBD and skeletal health: children are not small adults! Inflamm Bowel Dis 11:1020–1023

    Article  PubMed  Google Scholar 

  28. Haidar R, Musallam KM, Taher AT (2011) Bone disease and skeletal complications in patients with beta thalassemia major. Bone 48:425–432

    Article  PubMed  Google Scholar 

  29. Kaunitz AM, Shields WC (2005) Contraceptive equity and access in the United States: a 2005 update. Contraception 71:317–318

    Article  PubMed  Google Scholar 

  30. Lopez LM, Grimes DA, Schulz KF, Curtis KM (2011) Steroidal contraceptives: effect on bone fractures in women. Cochrane Database Syst Rev CD006033

  31. Lewiecki EM, Gordon CM, Baim S et al (2008) Special report on the 2007 adult and pediatric Position Development Conferences of the International Society for Clinical Densitometry. Osteoporos Int 19:1369–1378

    Article  PubMed  CAS  Google Scholar 

  32. Jager PL, Jonkman S, Koolhaas W, Stiekema A, Wolffenbuttel BH, Slart RH (2011) Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int 22:1059–1068

    Article  PubMed  CAS  Google Scholar 

  33. Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D (1997) Guidelines for diagnosis and management of osteoporosis. The European Foundation for Osteoporosis and Bone Disease. Osteoporos Int 7:390–406

    Article  PubMed  CAS  Google Scholar 

  34. Liu JM, Zhao HY, Ning G, Chen Y, Zhang LZ, Sun LH, Zhao YJ, Xu MY, Chen JL (2008) IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab 26:159–164

    Article  PubMed  CAS  Google Scholar 

  35. Diaz Curiel M, Garcia JJ, Carrasco JL, Honorato J, Perez Cano R, Rapado A, Alvarez Sanz C (2001) Prevalence of osteoporosis assessed by densitometry in the Spanish female population. Med Clin (Barc) 116:86–88

    CAS  Google Scholar 

  36. Bernstein CN, Blanchard JF, Leslie W, Wajda A, Yu BN (2000) The incidence of fracture among patients with inflammatory bowel disease. A population-based cohort study. Ann Intern Med 133:795–799

    PubMed  CAS  Google Scholar 

  37. Heijckmann AC, Huijberts MS, Schoon EJ et al (2008) High prevalence of morphometric vertebral deformities in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 20:740–747

    Article  PubMed  Google Scholar 

  38. Schulte CM (2004) Review article: bone disease in inflammatory bowel disease. Aliment Pharmacol Ther 20(Suppl 4):43–49

    Article  PubMed  Google Scholar 

  39. Thomason K, West J, Logan RF, Coupland C, Holmes GK (2003) Fracture experience of patients with coeliac disease: a population based survey. Gut 52:518–522

    Article  PubMed  CAS  Google Scholar 

  40. Ali T, Lam D, Bronze MS, Humphrey MB (2009) Osteoporosis in inflammatory bowel disease. Am J Med 122:599–604

    Article  PubMed  Google Scholar 

  41. Vestergaard P, Emborg C, Stoving RK, Hagen C, Mosekilde L, Brixen K (2002) Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders—a nationwide register study. Int J Eat Disord 32:301–308

    Article  PubMed  Google Scholar 

  42. Elkin SL, Fairney A, Burnett S, Kemp M, Kyd P, Burgess J, Compston JE, Hodson ME (2001) Vertebral deformities and low bone mineral density in adults with cystic fibrosis: a cross-sectional study. Osteoporos Int 12:366–372

    Article  PubMed  CAS  Google Scholar 

  43. Rossini M, Viapiana O, Del Marco A, de Terlizzi F, Gatti D, Adami S (2007) Quantitative ultrasound in adults with cystic fibrosis: correlation with bone mineral density and risk of vertebral fractures. Calcif Tissue Int 80:44–49

    Article  PubMed  CAS  Google Scholar 

  44. Sermet-Gaudelus I, Castanet M, Retsch-Bogart G, Aris RM (2009) Update on cystic fibrosis-related bone disease: a special focus on children. Paediatr Respir Rev 10:134–142

    Article  PubMed  Google Scholar 

  45. Ahmed LA, Joakimsen RM, Berntsen GK, Fonnebo V, Schirmer H (2006) Diabetes mellitus and the risk of non-vertebral fractures: the Tromso study. Osteoporos Int 17:495–500

    Article  PubMed  Google Scholar 

  46. Miao J, Brismar K, Nyren O, Ugarph-Morawski A, Ye W (2005) Elevated hip fracture risk in type 1 diabetic patients: a population-based cohort study in Sweden. Diabetes Care 28:2850–2855

    Article  PubMed  Google Scholar 

  47. Vestergaard P, Rejnmark L, Mosekilde L (2005) Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48:1292–1299

    Article  PubMed  CAS  Google Scholar 

  48. Burnham JM, Shults J, Weinstein R, Lewis JD, Leonard MB (2006) Childhood onset arthritis is associated with an increased risk of fracture: a population based study using the General Practice Research Database. Ann Rheum Dis 65:1074–1079

    Article  PubMed  CAS  Google Scholar 

  49. Legroux-Gerot I, Vignau J, Collier F, Cortet B (2005) Bone loss associated with anorexia nervosa. Joint Bone Spine 72:489–495

    Article  PubMed  Google Scholar 

  50. Lucas AR, Melton LJ 3rd, Crowson CS, O'Fallon WM (1999) Long-term fracture risk among women with anorexia nervosa: a population-based cohort study. Mayo Clin Proc 74:972–977

    PubMed  CAS  Google Scholar 

  51. Zipfel S, Herzog W, Beumont PJ, Russell J (2000) Osteoporosis. Eur Eat Disord Rev 8:108–116

    Article  Google Scholar 

  52. Bossu C, Galusca B, Normand S, Germain N, Collet P, Frere D, Lang F, Laville M, Estour B (2007) Energy expenditure adjusted for body composition differentiates constitutional thinness from both normal subjects and anorexia nervosa. Am J Physiol Endocrinol Metab 292:E132–E137

    Article  PubMed  CAS  Google Scholar 

  53. Fernandez-Garcia D, Rodriguez M, Garcia Aleman J, Garcia-Almeida JM, Picon MJ, Fernandez-Aranda F, Tinahones FJ (2009) Thin healthy women have a similar low bone mass to women with anorexia nervosa. Br J Nutr 102:709–714

    Article  PubMed  CAS  Google Scholar 

  54. Galusca B, Zouch M, Germain N, Bossu C, Frere D, Lang F, Lafage-Proust MH, Thomas T, Vico L, Estour B (2008) Constitutional thinness: unusual human phenotype of low bone quality. J Clin Endocrinol Metab 93:110–117

    Article  PubMed  CAS  Google Scholar 

  55. Chevalley T, Bonjour JP, Ferrari S, Rizzoli R (2008) Influence of age at menarche on forearm bone microstructure in healthy young women. J Clin Endocrinol Metab 93:2594–2601

    Article  PubMed  CAS  Google Scholar 

  56. Khosla S, Lufkin EG, Hodgson SF, Fitzpatrick LA, Melton LJ 3rd (1994) Epidemiology and clinical features of osteoporosis in young individuals. Bone 15:551–555

    Article  PubMed  CAS  Google Scholar 

  57. Moreira Kulak CA, Schussheim DH, McMahon DJ, Kurland E, Silverberg SJ, Siris ES, Bilezikian JP, Shane E (2000) Osteoporosis and low bone mass in premenopausal and perimenopausal women. Endocr Pract 6:296–304

    PubMed  CAS  Google Scholar 

  58. Peris P, Guanabens N, Martinez de Osaba MJ, Monegal A, Alvarez L, Pons F, Ros I, Cerda D, Munoz-Gomez J (2002) Clinical characteristics and etiologic factors of premenopausal osteoporosis in a group of Spanish women. Semin Arthritis Rheum 32:64–70

    Article  PubMed  Google Scholar 

  59. Leffler DA, Schuppan D (2010) Update on serologic testing in celiac disease. Am J Gastroenterol 105:2520–2524

    Article  PubMed  Google Scholar 

  60. Kann PH, Pfutzner A, Delling G, Schulz G, Meyer S (2006) Transiliac bone biopsy in osteoporosis: frequency, indications, consequences and complications. An evaluation of 99 consecutive cases over a period of 14 years. Clin Rheumatol 25:30–34

    Article  PubMed  CAS  Google Scholar 

  61. Bains SN, Hsieh FH (2010) Current approaches to the diagnosis and treatment of systemic mastocytosis. Ann Allergy Asthma Immunol 104:1–10, quiz 10–12, 41

    Article  PubMed  Google Scholar 

  62. Barete S, Assous N, de Gennes C et al (2010) Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 69:1838–1841

    Article  PubMed  CAS  Google Scholar 

  63. Vasikaran S, Eastell R, Bruyere O et al (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420

    Article  PubMed  CAS  Google Scholar 

  64. Glover SJ, Gall M, Schoenborn-Kellenberger O, Wagener M, Garnero P, Boonen S, Cauley JA, Black DM, Delmas PD, Eastell R (2009) Establishing a reference interval for bone turnover markers in 637 healthy, young, premenopausal women from the United Kingdom, France, Belgium, and the United States. J Bone Miner Res 24:389–397

    Article  PubMed  Google Scholar 

  65. Dresner-Pollak R, Karmeli F, Eliakim R, Ackerman Z, Rachmilewitz D (2000) Increased urinary N-telopeptide cross-linked type 1 collagen predicts bone loss in patients with inflammatory bowel disease. Am J Gastroenterol 95:699–704

    Article  PubMed  CAS  Google Scholar 

  66. Adami S, Bertoldo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Battista Rini G (2009) 25-Hydroxy vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 45:423–426

    Article  PubMed  CAS  Google Scholar 

  67. Adami S, Bianchi G, Brandi ML, Giannini S, Ortolani S, DiMunno O, Frediani B, Rossini M (2008) Determinants of bone turnover markers in healthy premenopausal women. Calcif Tissue Int 82:341–347

    Article  PubMed  CAS  Google Scholar 

  68. Adami S, Gatti D, Viapiana O, Fiore CE, Nuti R, Luisetto G, Ponte M, Rossini M (2008) Physical activity and bone turnover markers: a cross-sectional and a longitudinal study. Calcif Tissue Int 83:388–392

    Article  PubMed  CAS  Google Scholar 

  69. Adami S, Zivelonghi A, Braga V, Fracassi E, Gatti D, Rossini M, Ulivieri FM, Viapiana O (2010) Insulin-like growth factor-1 is associated with bone formation markers, PTH and bone mineral density in healthy premenopausal women. Bone 46:244–247

    Article  PubMed  CAS  Google Scholar 

  70. Cohen A, Dempster DW, Recker RR et al (2011) Abnormal bone microarchitecture and evidence of osteoblast dysfunction in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab 96:3095–3105

    Article  PubMed  CAS  Google Scholar 

  71. Maggio AB, Ferrari S, Kraenzlin M, Marchand LM, Schwitzgebel V, Beghetti M, Rizzoli R, Farpour-Lambert NJ (2010) Decreased bone turnover in children and adolescents with well controlled type 1 diabetes. J Pediatr Endocrinol Metab 23:697–707

    Article  PubMed  CAS  Google Scholar 

  72. Garnero P, Schott AM, Prockop D, Chevrel G (2009) Bone turnover and type I collagen C-telopeptide isomerization in adult osteogenesis imperfecta: associations with collagen gene mutations. Bone 44:461–466

    Article  PubMed  CAS  Google Scholar 

  73. Cohen A, Shane E (2008) Treatment of premenopausal women with low bone mineral density. Curr Osteoporos Rep 6:39–46

    Article  PubMed  Google Scholar 

  74. Superti-Furga A, Unger S (2007) Nosology and classification of genetic skeletal disorders: 2006 revision. Am J Med Genet A 143:1–18

    PubMed  Google Scholar 

  75. Finkelstein JS, Klibanski A, Arnold AL, Toth TL, Hornstein MD, Neer RM (1998) Prevention of estrogen deficiency-related bone loss with human parathyroid hormone-(1–34): a randomized controlled trial. JAMA 280:1067–1073

    Article  PubMed  CAS  Google Scholar 

  76. Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K (1995) Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 80:3689–3698

    Article  PubMed  CAS  Google Scholar 

  77. Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS (1994) Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 331:1056–1061

    Article  PubMed  CAS  Google Scholar 

  78. Mornet E (2007) Hypophosphatasia. Orphanet J Rare Dis 2:40

    Article  PubMed  Google Scholar 

  79. Gong Y, Slee RB, Fukai N et al (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523

    Article  PubMed  CAS  Google Scholar 

  80. Bishop N (2009) Primary osteoporosis. Endocr Dev 16:157–169

    Article  PubMed  Google Scholar 

  81. Ostertag A, Cohen-Solal M, Audran M, Legrand E, Marty C, Chappard D, de Vernejoul MC (2009) Vertebral fractures are associated with increased cortical porosity in iliac crest bone biopsy of men with idiopathic osteoporosis. Bone 44:413–417

    Article  PubMed  Google Scholar 

  82. Van Pottelbergh I, Goemaere S, Zmierczak H, De Bacquer D, Kaufman JM (2003) Deficient acquisition of bone during maturation underlies idiopathic osteoporosis in men: evidence from a three-generation family study. J Bone Miner Res 18:303–311

    Article  PubMed  Google Scholar 

  83. Ferrari SL, Deutsch S, Baudoin C, Cohen-Solal M, Ostertag A, Antonarakis SE, Rizzoli R, de Vernejoul MC (2005) LRP5 gene polymorphisms and idiopathic osteoporosis in men. Bone 37:770–775

    Article  PubMed  CAS  Google Scholar 

  84. Rubin MR, Schussheim DH, Kulak CA, Kurland ES, Rosen CJ, Bilezikian JP, Shane E (2005) Idiopathic osteoporosis in premenopausal women. Osteoporos Int 16:526–533

    Article  PubMed  Google Scholar 

  85. Peris P, Martinez-Ferrer A, Monegal A, Martinez de Osaba MJ, Alvarez L, Ros I, Muxi A, Reyes R, Guanabens N (2008) Aetiology and clinical characteristics of male osteoporosis. Have they changed in the last few years? Clin Exp Rheumatol 26:582–588

    PubMed  CAS  Google Scholar 

  86. Kovacs CS (2005) Calcium and bone metabolism during pregnancy and lactation. J Mammary Gland Biol Neoplasia 10:105–118

    Article  PubMed  Google Scholar 

  87. Oliveri B, Parisi MS, Zeni S, Mautalen C (2004) Mineral and bone mass changes during pregnancy and lactation. Nutrition 20:235–240

    Article  PubMed  CAS  Google Scholar 

  88. Kent GN, Price RI, Gutteridge DH, Rosman KJ, Smith M, Allen JR, Hickling CJ, Blakeman SL (1991) The efficiency of intestinal calcium absorption is increased in late pregnancy but not in established lactation. Calcif Tissue Int 48:293–295

    Article  PubMed  CAS  Google Scholar 

  89. Kovacs CS (2001) Calcium and bone metabolism in pregnancy and lactation. J Clin Endocrinol Metab 86:2344–2348

    Article  PubMed  CAS  Google Scholar 

  90. Kovacs CS, Fuleihan Gel H (2006) Calcium and bone disorders during pregnancy and lactation. Endocrinol Metab Clin N Am 35:21–51

    Article  CAS  Google Scholar 

  91. Sowers M, Corton G, Shapiro B, Jannausch ML, Crutchfield M, Smith ML, Randolph JF, Hollis B (1993) Changes in bone density with lactation. JAMA 269:3130–3135

    Article  PubMed  CAS  Google Scholar 

  92. Bianchi ML (2009) Osteoporosis during pregnancy. Eur Musculoskel Rev 4:30–34

    Google Scholar 

  93. Csotye J, Sisak K, Bardocz L, Toth K (2010) Bilateral spontaneous displaced femoral neck fractures during pregnancy. J Trauma 68:E115–E116

    Article  PubMed  Google Scholar 

  94. Khovidhunkit W, Epstein S (1996) Osteoporosis in pregnancy. Osteoporos Int 6:345–354

    Article  PubMed  CAS  Google Scholar 

  95. Kalkwarf HJ, Specker BL, Bianchi DC, Ranz J, Ho M (1997) The effect of calcium supplementation on bone density during lactation and after weaning. N Engl J Med 337:523–528

    Article  PubMed  CAS  Google Scholar 

  96. Mauro M, Radovic V, Armstrong D (2007) Improvement of lumbar bone mass after infliximab therapy in Crohn's disease patients. Can J Gastroenterol 21:637–642

    PubMed  Google Scholar 

  97. Pazianas M, Rhim AD, Weinberg AM, Su C, Lichtenstein GR (2006) The effect of anti-TNF-alpha therapy on spinal bone mineral density in patients with Crohn's disease. Ann N Y Acad Sci 1068:543–556

    Article  PubMed  CAS  Google Scholar 

  98. Haugeberg G, Conaghan PG, Quinn M, Emery P (2009) Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study. Ann Rheum Dis 68:1898–1901

    Article  PubMed  CAS  Google Scholar 

  99. Kemppainen T, Kroger H, Janatuinen E et al (1999) Bone recovery after a gluten-free diet: a 5-year follow-up study. Bone 25:355–360

    Article  PubMed  CAS  Google Scholar 

  100. Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A (2002) Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab 87:2883–2891

    Article  PubMed  CAS  Google Scholar 

  101. Sim LA, McGovern L, Elamin MB, Swiglo BA, Erwin PJ, Montori VM (2010) Effect on bone health of estrogen preparations in premenopausal women with anorexia nervosa: a systematic review and meta-analyses. Int J Eat Disord 43:218–225

    PubMed  Google Scholar 

  102. Hoy J (2011) Bone, fracture and frailty. Curr Opin HIV AIDS 6:309–314

    Article  PubMed  Google Scholar 

  103. Miller KK, Grieco KA, Mulder J, Grinspoon S, Mickley D, Yehezkel R, Herzog DB, Klibanski A (2004) Effects of risedronate on bone density in anorexia nervosa. J Clin Endocrinol Metab 89:3903–3906

    Article  PubMed  CAS  Google Scholar 

  104. Delmas PD, Balena R, Confravreux E, Hardouin C, Hardy P, Bremond A (1997) Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study. J Clin Oncol 15:955–962

    PubMed  CAS  Google Scholar 

  105. Fuleihan Gel H, Salamoun M, Mourad YA, Chehal A, Salem Z, Mahfoud Z, Shamseddine A (2005) Pamidronate in the prevention of chemotherapy-induced bone loss in premenopausal women with breast cancer: a randomized controlled trial. J Clin Endocrinol Metab 90:3209–3214

    Article  CAS  Google Scholar 

  106. Saarto T, Blomqvist C, Valimaki M, Makela P, Sarna S, Elomaa I (1997) Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients. J Clin Oncol 15:1341–1347

    PubMed  CAS  Google Scholar 

  107. Vehmanen L, Elomaa I, Blomqvist C, Saarto T (2006) Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status. J Clin Oncol 24:675–680

    Article  PubMed  CAS  Google Scholar 

  108. Tauchmanova L, De Simone G, Musella T, Orio F, Ricci P, Nappi C, Lombardi G, Colao A, Rotoli B, Selleri C (2006) Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation. Bone Marrow Transplant 37:81–88

    PubMed  CAS  Google Scholar 

  109. Sagsveen M, Farmer JE, Prentice A, Breeze A (2003) Gonadotrophin-releasing hormone analogues for endometriosis: bone mineral density. Cochrane Database Syst Rev CD001297

  110. Chapman I, Greville H, Ebeling PR, King SJ, Kotsimbos T, Nugent P, Player R, Topliss DJ, Warner J, Wilson JW (2009) Intravenous zoledronate improves bone density in adults with cystic fibrosis (CF). Clin Endocrinol (Oxf) 70:838–846

    Article  CAS  Google Scholar 

  111. Conwell LS, Chang AB (2009) Bisphosphonates for osteoporosis in people with cystic fibrosis. Cochrane Database Syst Rev CD002010

  112. Papaioannou A, Kennedy CC, Freitag A et al (2008) Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial). Chest 134:794–800

    Article  PubMed  CAS  Google Scholar 

  113. Gilfillan CP, Strauss BJ, Rodda CP, Bowden DK, Kean AM, Obaid M, Crawford BA (2006) A randomized, double-blind, placebo-controlled trial of intravenous zoledronic acid in the treatment of thalassemia-associated osteopenia. Calcif Tissue Int 79:138–144

    Article  PubMed  CAS  Google Scholar 

  114. Voskaridou E, Christoulas D, Konstantinidou M, Tsiftsakis E, Alexakos P, Terpos E (2008) Continuous improvement of bone mineral density two years post zoledronic acid discontinuation in patients with thalassemia-induced osteoporosis: long-term follow-up of a randomized, placebo-controlled trial. Haematologica 93:1588–1590

    Article  PubMed  CAS  Google Scholar 

  115. Mamtani M, Kulkarni H (2010) Bone recovery after zoledronate therapy in thalassemia-induced osteoporosis: a meta-analysis and systematic review. Osteoporos Int 21:183–187

    Article  PubMed  CAS  Google Scholar 

  116. Laroche M, Livideanu C, Paul C, Cantagrel A (2011) Interferon alpha and pamidronate in osteoporosis with fracture secondary to mastocytosis. Am J Med 124:776–778

    Article  PubMed  CAS  Google Scholar 

  117. Bolland MJ, Grey A, Horne AM, Briggs SE, Thomas MG, Ellis-Pegler RB, Gamble GD, Reid IR (2012) Effects of intravenous zoledronate on bone turnover and bone density persist for at least five years in HIV-infected men. J Clin Endocrinol Metab

  118. Huang J, Meixner L, Fernandez S, McCutchan JA (2009) A double-blinded, randomized controlled trial of zoledronate therapy for HIV-associated osteopenia and osteoporosis. AIDS 23:51–57

    Article  PubMed  CAS  Google Scholar 

  119. Rozenberg S, Lanoy E, Bentata M et al (2012) Effect of alendronate on HIV-associated osteoporosis: a randomized, double-blind, placebo-controlled, 96-week trial (ANRS 120). AIDS Res Hum Retroviruses

  120. Rauch F, Glorieux FH (2006) Treatment of children with osteogenesis imperfecta. Curr Osteoporos Rep 4:159–164

    Article  PubMed  Google Scholar 

  121. Shapiro JR, Thompson CB, Wu Y, Nunes M, Gillen C (2010) Bone mineral density and fracture rate in response to intravenous and oral bisphosphonates in adult osteogenesis imperfecta. Calcif Tissue Int 87:120–129

    Article  PubMed  CAS  Google Scholar 

  122. Devogelaer JP, Goemaere S, Boonen S, Body JJ, Kaufman JM, Reginster JY, Rozenberg S, Boutsen Y (2006) Evidence-based guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis: a consensus document of the Belgian Bone Club. Osteoporos Int 17:8–19

    Article  PubMed  CAS  Google Scholar 

  123. Grossman JM, Gordon R, Ranganath VK et al (2010) American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 62:1515–1526

    Article  Google Scholar 

  124. Lekamwasam S, Adachi JD, Agnusdei D, et al. (2012) A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos Int

  125. Losada I, Sartori L, Di Gianantonio E, Zen M, Clementi M, Doria A (2010) Bisphosphonates in patients with autoimmune rheumatic diseases: can they be used in women of childbearing age? Autoimmun Rev 9:547–552

    Article  PubMed  CAS  Google Scholar 

  126. Biswas PN, Wilton LV, Shakir SA (2003) Pharmacovigilance study of alendronate in England. Osteoporos Int 14:507–514

    Article  PubMed  CAS  Google Scholar 

  127. Chan B, Zacharin M (2006) Maternal and infant outcome after pamidronate treatment of polyostotic fibrous dysplasia and osteogenesis imperfecta before conception: a report of four cases. J Clin Endocrinol Metab 91:2017–2020

    Article  PubMed  CAS  Google Scholar 

  128. Djokanovic N, Klieger-Grossmann C, Koren G (2008) Does treatment with bisphosphonates endanger the human pregnancy? J Obstet Gynaecol Can 30:1146–1148

    PubMed  Google Scholar 

  129. Illidge TM, Hussey M, Godden CW (1996) Malignant hypercalcaemia in pregnancy and antenatal administration of intravenous pamidronate. Clin Oncol (R Coll Radiol) 8:257–258

    Article  CAS  Google Scholar 

  130. Munns CF, Rauch F, Ward L, Glorieux FH (2004) Maternal and fetal outcome after long-term pamidronate treatment before conception: a report of two cases. J Bone Miner Res 19:1742–1745

    Article  PubMed  Google Scholar 

  131. O'Sullivan SM, Grey AB, Singh R, Reid IR (2006) Bisphosphonates in pregnancy and lactation-associated osteoporosis. Osteoporos Int 17:1008–1012

    Article  PubMed  CAS  Google Scholar 

  132. Patlas N, Golomb G, Yaffe P, Pinto T, Breuer E, Ornoy A (1999) Transplacental effects of bisphosphonates on fetal skeletal ossification and mineralization in rats. Teratology 60:68–73

    Article  PubMed  CAS  Google Scholar 

  133. McKenzie AF, Budd RS, Yang C, Shapiro B, Hicks RJ (1994) Technetium-99 m-methylene diphosphonate uptake in the fetal skeleton at 30 weeks gestation. J Nucl Med 35:1338–1341

    PubMed  CAS  Google Scholar 

  134. Cohen A, Liu XS, Stein EM, McMahon DJ, Rogers HF, Lemaster J, Recker RR, Lappe JM, Guo XE, Shane E (2009) Bone microarchitecture and stiffness in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab 94:4351–4360

    Article  PubMed  CAS  Google Scholar 

  135. Thayu M, Shults J, Zemel B, Baldassano R, Lewis J, Leonard M (2009) Improvements in trabecular density, cortical dimensions, and a bone formation biomarker after initiation of infliximab therapy for childhood Crohn disease. J Bone Miner Res 24(Suppl1):S1072

    Google Scholar 

  136. Gnant MF, Mlineritsch B, Luschin-Ebengreuth G et al (2007) Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 25:820–828

    Article  PubMed  CAS  Google Scholar 

  137. Misra M, Prabhakaran R, Miller KK et al (2008) Weight gain and restoration of menses as predictors of bone mineral density change in adolescent girls with anorexia nervosa-1. J Clin Endocrinol Metab 93:1231–1237

    Article  PubMed  CAS  Google Scholar 

  138. Golden NH, Iglesias EA, Jacobson MS, Carey D, Meyer W, Schebendach J, Hertz S, Shenker IR (2005) Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab 90:3179–3185

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank P. Devogelaer, C. Gluer, E. Orwoll, P. Miller, and other IOF CSA members for their valuable comments on the manuscript, as well as D. Pierroz for her editorial assistance.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Division of Bone Diseases, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland

    S. Ferrari

  2. Bone Metabolism Unit, Istituto Auxologico Italiano IRCCS, Milan, Italy

    M. L. Bianchi

  3. Garvan Institute of Medical Research, St Vincent’s Hospital, University of New South Wales, Sydney, NSW, Australia

    J. A. Eisman

  4. Osteoporosis Center, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel

    A. J. Foldes

  5. Rheumatology Unit, University of Verona, Verona, Italy

    S. Adami

  6. International Osteoporosis Foundation, Nyon, Switzerland

    D. A. Wahl

  7. Institute of Rheumatology and Department of Rheumatology, Faculty of Medicine, Charles University, Prague, Czech Republic

    J. J. Stepan

  8. Federation of Rheumatology, Hospital Lariboisière, University Paris 7, Paris, France

    M.-C. de Vernejoul

  9. Department of Endocrinology and Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Ghent, Belgium

    J.-M. Kaufman

Authors
  1. S. Ferrari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. L. Bianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. A. Eisman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. J. Foldes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Adami
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. A. Wahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. J. Stepan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M.-C. de Vernejoul
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J.-M. Kaufman
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

For the IOF Committee of Scientific Advisors Working Group on Osteoporosis Pathophysiology

Corresponding author

Correspondence to S. Ferrari.

Additional information

This review paper has been endorsed by the Committee of Scientific Advisors of the IOF

Appendix A. Effects of treatments (specific and bone drugs) on the various diseases

Appendix A. Effects of treatments (specific and bone drugs) on the various diseases

Secondary disease

Treatment

Benefits on bone

Reference

Inflammatory bowel disease: Crohn's disease

Infliximab

Tibia trabecular BMD and endosteal circumference Z-scores improved significantly over 12 months in childhood Crohn's disease

[135]

Infliximab

LS BMD: +8.13 % after 1 year follow up compared to baseline, vs. only +1.55 % in the control group (p < 0.01)

[96]

Infliximab + bisphosphonates

LS BMD: +6.7 %/year in patients on concurrent treatment vs. +4.46 %/year in those on oral bisphosphonates alone (p = 0.045) over 2.2 + 0.99 years

[97]

Celiac disease

Gluten-free diet

4 % increase in LS and FN BMD after 1 year compared to baseline and up to 8 % for trochanter BMD. Lower values after 5-year follow-up

[99]

Cystic fibrosis

Alendronate

After 1 year of alendronate (70 mg once weekly for 1 year), BMD increased at the lumbar spine (5.2 % vs. −0.1 %) and at the hip (2.1 % vs. −1.3 %) compared with controls

[111, 112]

Zoledronic acid

Compared with controls, LS BMD in zoledronic-treated group (2 mg i.v. every 3 months for 2 years) increased from baseline at 1 year (6.6 % vs. 0.35 %) and 2 years (6.14 % vs. 0.44 %), and femoral neck BMD increased at 1 year (4.12 % vs. −1.59 %) and 2 years (4.23 % vs. −2.5 %)

[110]

Adjuvant endocrine therapy for hormone-responsive breast cancer

Zoledronic acid

Zoledronic acid (4 mg intravenously every 6 months for 3 years) prevented bone loss at the spine and hip

[104, 136]

Risedronate

In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group (30 mg/d, oral for 2 weeks, followed by 10 weeks without drug, repeated 8 times over 2 years). At 2 years, the mean difference (±SEM) between groups was 2.5 % ± 1.2 % at the lumbar spine (p = .041) and 2.6 % ± 1.1 %, (95 % CI, 0.3 to 4.8) at the femoral neck (p = .029)

Ovarian failure after allogeneic stem cell transplantation

Various (Ca + Vit. D; HRT, risedronate, zoledronic acid)

At 1 year, a significant decrease in LS and FN BMD was observed for the Ca + Vit. D group and a milder decrease in the HRT group. Risedronate treatment increased significantly LS BMD and prevented FN BMD loss. Zoledronic acid increased significantly both LS and FN BMD

[108]

Anorexia nervosa

Menstrual recovery

Stabilization of BMD with menstrual recovery

[137]

Recombinant human IGF-I and HRT

BMD increased in women treated with rhIGF-I and HRT (1.8 %) vs. rhIGF-I alone (0.3 %)

[100]

Risedronate

Increase of spine BMD of 4.9 ± 1.0 % at 9 months (5 mg daily), even without significant weight gain

[103]

Alendronate

Body weight was the most important determinant of BMD after 1 year of alendronate (10 mg/d oral)

[138]

Chemo-induced amenorrhea

Tamoxifen

At 3 years of follow-up, in amenorrheic patients who developed chemotherapy-induced early menopause, the LS BMD decreased −6.8 % in tamoxifen users and −9.5 % in the controls

[107]

Pamidronate

At 1 year of follow-up of pamidronate (60 mg i.v. every 3 months), in amenorrheic patients who developed chemotherapy-induced early menopause, the LS BMD increased 1 % in tamoxifen users and decreased −4 % in the controls

[105]

Rheumatoid arthritis

Infliximab

At 1 year of follow-up, BMD loss was significantly reduced in the infliximab group compared with the placebo group at the femoral neck (−0.35 % vs. −3.43 %) and total hip (−0.23 % vs. −2.62 %) but not at the hand and spine

[98]

HIV

Alendronate

Alendronate (70 mg weekly for 96 weeks) increased BMD at sites with a T-score < −2.5 by 7.1 % vs. 1.0 % in the placebo (p = 0.0003)

[119]

Zoledronic acid

Bone density improved in a 12-month trial of 5 mg intravenous zoledronate compared to placebo

[118]

Zoledronic acid

Between 2 and 6 years, after the second dose of zoledronic acid (4 mg intravenously yearly), LS BMD was greater by 3.7 % compared to placebo (p = 0.03), as well as FN BMD and total body BMD

[117]

Thalassemia

Zoledronic acid

LS BMD was 8.9 % greater in patients treated for 2 years with 4 mg i.v. zoledronic acid every 3 months compared to placebo

[113]

Zoledronic acid

At 2 years of follow-up, after 4 mg i.v. zoledronic acid every 3or 6 months for a year, BMD was significantly increased at all sites compared to baseline (p < 0.01)

[114]

Zoledronic acid

Zoledronic acid improved BMD by 0.69 SD (95 % confidence interval 0.47–0.90)

[115]

See text for details

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferrari, S., Bianchi, M.L., Eisman, J.A. et al. Osteoporosis in young adults: pathophysiology, diagnosis, and management. Osteoporos Int 23, 2735–2748 (2012). https://doi.org/10.1007/s00198-012-2030-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-012-2030-x

Keywords

Search

Navigation