Skip to main content
SpringerLink
Log in

Monoclonal gammopathy of undetermined significance and bone health outcomes: a systematic review and exploratory meta-analysis

  • Short Communication
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a common condition in the elderly. A number of studies have investigated the relationship between MGUS and bone health outcomes including bone mineral density (BMD), osteoporosis and fractures, but no meta-analysis exists. We conducted a systematic review and exploratory meta-analysis comparing bone health outcomes in patients with MGUS. Two independent authors searched PubMed and Scopus from inception until 19 October 2016. A meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD was conducted. Standardised mean differences (SMD) ± 95% confidence intervals (CIs) were calculated for BMD, and risk ratios (RRs) were calculated for prevalent and incident fractures. Of 174 initial hits, 10 studies of moderate methodological quality were eligible, including 8711 individuals with MGUS vs. 52,865 controls. Compared to controls, subjects with MGUS showed significantly lower values for radial cortical volumetric BMD (1 study; SMD = −5.45, 95% CI: −7.24 to −3.66), but not at the lumbar spine, femoral neck or hip. The incidence of fractures was higher in people with MGUS (n = 7466) vs. controls (n = 52,304) (RR = 1.36, 95% CI 1.28–1.44, I 2 = 0%) over a median of 12.5-year follow-up. The incidence of vertebral fractures was particularly elevated (RR = 2.50, 95% CI 1.53–4.06) although limited to two studies. In conclusion, although with limitations, our preliminary meta-analysis suggests that patients with MGUS are at higher risk of fractures despite evidence for differences in BMD being equivocal. Future longitudinal research is required to confirm our findings and determine if fracture prevention interventions are warranted in people with MGUS.

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

References

  1. Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kröger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet-Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M, International Myeloma Working Group (2010) Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 24:1121–1127. doi:10.1038/leu.2010.60

    Article  CAS  PubMed  Google Scholar 

  2. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, Dispenzieri A, Katzmann JA, Melton LJ 3rd (2006) Prevalence of monoclonal gammopathy of undetermined significance. New Eng J Med 354:1362–1369. doi:10.1056/NEJMoa054494

    Article  CAS  PubMed  Google Scholar 

  3. Drake MT (2014) unveiling skeletal fragility in patients diagnosed with MGUS: no longer a condition of undetermined significance? J Bone Miner Res Off J Am Soc Bone Miner Res 29:2529–2533. doi:10.1002/jbmr.2387

    Article  Google Scholar 

  4. Drake MT (2009) Bone disease in multiple myeloma. Oncology (Williston Park, NY) 23:28–32

    Google Scholar 

  5. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6:e1000100. doi:10.1371/journal.pmed.1000100

    Article  PubMed  PubMed Central  Google Scholar 

  6. Organization WH (2004) Who scientific group on the assessment of osteoporosis at primary health care level. World Health Org. doi:10.1016/S0140-6736(02)08761-5

    Google Scholar 

  7. Wells G, Shea BJ, O'Connell D, je Peterson, Welch V, Losos M, Tugwell P (2012) The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. (http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp) 2012. doi:10.2307/632432. Accessed 20 July 2016

  8. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188. doi:10.1016/0197-2456(86)90046-2

    Article  CAS  PubMed  Google Scholar 

  9. Higgins JPT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. doi:10.1002/sim.1186

    Article  PubMed  Google Scholar 

  10. Dizdar O, Erman M, Cankurtaran M, Halil M, Ulger Z, Yavuz BB, Ariogul S, Pınar A, Harputluoglu H, Kars A, Çelik İ (2008) Lower bone mineral density in geriatric patients with monoclonal gammopathy of undetermined significance. Ann Hematol 87:57–60. doi:10.1007/s00277-007-0376-5

    Article  PubMed  Google Scholar 

  11. Ng AC, Khosla S, Charatcharoenwitthaya N, Kumar SK, Achenbach SJ, Holets MF, McCready LK, Melton LJ 3rd, Kyle RA, Rajkumar SV, Drake MT (2011) Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1α levels in patients with MGUS. Blood 118:6529–6534. doi:10.1182/blood-2011-04-351437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pepe J, Petrucci MT, Nofroni I, Fassino V, Diacinti D, Romagnoli E, Minisola S (2006) Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance. Br J Haematol 134:485–490. doi:10.1111/j.1365-2141.2006.06217.x

    Article  PubMed  Google Scholar 

  13. Abrahamsen B, Andersen I, Christensen SS, Madsen JS, Brixen K (2005) Utility of testing for monoclonal bands in serum of patients with suspected osteoporosis: retrospective, cross sectional study. BMJ 330:818. doi:10.1136/bmj.38376.401701.8F (clinical research ed)

    Article  PubMed  PubMed Central  Google Scholar 

  14. Golombick T, Diamond T (2008) Prevalence of monoclonal gammopathy of undetermined significance/myeloma in patients with acute osteoporotic vertebral fractures. Acta Haematol 120:87–90. doi:10.1159/000162282

    Article  PubMed  Google Scholar 

  15. Piot JM, Royer M, Schmidt-Tanguy A, Hoppé E, Gardembas M, Bourrée T, Hunault M, François S, Boyer F, Ifrah N, Renier G, Chevailler A, Audran M, Chappard D, Libouban H, Mabilleau G, Legrand E, Bouvard B (2015) Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance. Blood Cancer J 5:e345. doi:10.1038/bcj.2015.71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bida JP, Kyle RA, Therneau TM, Melton LJ 3rd, Plevak MF, Larson DR, Dispenzieri A, Katzmann JA, Rajkumar SV (2009) Disease associations with monoclonal gammopathy of undetermined significance: a population-based study of 17,398 patients. Mayo Clin Proc 84:685–693. doi:10.1016/S0025-6196(11)60518-1

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O (2010) Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study. Blood 116:2651–2655. doi:10.1182/blood-2010-04-282848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gregersen H, Jensen P, Gislum M, Jørgensen B, Sørensen HT, Nørgaard M (2006) Fracture risk in patients with monoclonal gammopathy of undetermined significance. Br J Haematol 135:62–67. doi:10.1111/j.1365-2141.2006.06269.x

    Article  PubMed  Google Scholar 

  19. Malgo F, Appelman-Dijkstra NM, Termaat MF, van der Heide HJL, Schipper IB, Rabelink TJ, Hamdy NAT (2016) High prevalence of secondary factors for bone fragility in patients with a recent fracture independently of BMD. Arch Osteoporos 11:1–8. doi:10.1007/s11657-016-0258-3

    Article  Google Scholar 

  20. Seeman E, Delmas PD (2006) Bone quality–the material and structural basis of bone strength and fragility. New Eng J Med 354:2250–2261. doi:10.1056/NEJMra053077

    Article  CAS  PubMed  Google Scholar 

  21. Walker RE, Lawson MA, Buckle CH, Snowden JA, Chantry AD (2014) Myeloma bone disease: pathogenesis, current treatments and future targets. Br Med Bull 111:117–138. doi:10.1093/bmb/ldu016

    Article  CAS  PubMed  Google Scholar 

  22. Dalton JE, Bolen SD, Mascha EJ (2016) Publication bias: the elephant in the review. Anesth Analg 123:812–3

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Geriatrics Section, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy

    Nicola Veronese, Giuseppe Sergi & Enzo Manzato

  2. Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy

    Claudio Luchini

  3. Department of Neurosciences, University of Padova, Padua, Italy

    Marco Solmi

  4. Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK

    Brendon Stubbs

  5. Health Service and Population Research Department, Institute of Psychiatry, King’s College London, De Crespigny Park, London, SE5 8AF, UK

    Brendon Stubbs

  6. Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK

    Brendon Stubbs

Authors
  1. Nicola Veronese
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claudio Luchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marco Solmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuseppe Sergi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Enzo Manzato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Brendon Stubbs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicola Veronese.

Ethics declarations

Financial disclosure

None.

Conflict of interest

All authors have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 93 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Veronese, N., Luchini, C., Solmi, M. et al. Monoclonal gammopathy of undetermined significance and bone health outcomes: a systematic review and exploratory meta-analysis. J Bone Miner Metab 36, 128–132 (2018). https://doi.org/10.1007/s00774-017-0817-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-017-0817-8

Keywords

Search

Navigation