Osteoporosis in young adults: pathophysiology, diagnosis, and management

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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.

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Notes

  1. 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 [5254].

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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.

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Correspondence to S. Ferrari.

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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]

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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

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Keywords

  • Diagnosis
  • IOF
  • Low bone mass
  • Osteoporosis
  • Secondary osteoporosis
  • Young adults