Correspondence

Monoclonal Gammopathy of Undetermined Significance

N Engl J Med 2007; 356:2223-2224May 24, 2007

Article

To the Editor:

In the article concerning monoclonal gammopathy of undetermined significance (MGUS) (Dec. 28 issue),1 Bladé disregards a complication that is especially important in clinical practice. Indeed, the problem of skeletal involvement in this disease should not be viewed only as a way to rule out lytic lesions but should be placed in a more comprehensive context. We2 and others3 have reported an increased rate of vertebral fractures among patients with MGUS. This increase is probably secondary to an altered balance between the receptor activator of nuclear factor–κB ligand (RANKL) and osteoprotegerin.2,4 This is important for two reasons. First, a vertebral fracture is associated with an increased risk of other axial fractures, independently of bone mass. Second, patients with fractures should be offered drugs, such as bisphosphonates, that have demonstrated effectiveness in the secondary prevention of axial fractures. Along these lines, if an excess of RANKL activity is the pathophysiological mechanism underlying bone loss, other molecules, such as denosumab,5 will prove to be effective in the future.

Salvatore Minisola, M.D.
Jessica Pepe, M.D.
Elisabetta Romagnoli, M.D.
University of Rome La Sapienza, 00161 Rome, Italy
salvatore.minisola@fastwebnet.it

5 References

1. 1

   Blade J. Monoclonal gammopathy of undetermined significance. N Engl J Med 2006;355:2765-2770
   Full Text | Web of Science | Medline

2. 2

   Pepe J, Petrucci MT, Nofroni I, et al. Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance. Br J Haematol 2006;134:485-490
   CrossRef | Web of Science | Medline

3. 3

   Melton LJ III, Rajkumar SV, Khosla S, Achenbach SJ, Oberg AL, Kyle RA. Fracture risk in monoclonal gammopathy of undetermined significance. J Bone Miner Res 2004;19:25-30
   CrossRef | Web of Science | Medline

4. 4

   Politou M, Terpos E, Anagnostopoulos A, et al. Role of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin and macrophage protein 1-alpha (MIP-1a) in monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol 2004;126:686-689
   CrossRef | Web of Science | Medline

5. 5

   McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006;354:821-831
   Full Text | Web of Science | Medline

Author/Editor Response

Minisola et al. emphasize that the Mayo Clinic group1 and their group2 have reported an increased incidence of vertebral fractures among patients with MGUS. In contrast, Politou et al.3 reported that the increased bone resorption observed in MGUS is compensated for by new bone formation; in their study, none of the patients with MGUS had apparent radiographic evidence of osteoporosis or osteopenia (although it should be recognized that this assessment was based on a skeletal survey only).

Pending further data on the risk of fracture among patients with MGUS, I would recommend that the decision to measure bone mineral density in patients with MGUS be made in accordance with the usual guidelines for the population (e.g., those of the National Osteoporosis Foundation4) and be predicated on the presence of other risk factors for bone loss. Likewise, treatment should be administered according to the current indications for the treatment of bone loss in the general population. The cost and possible long-term adverse effects in an asymptomatic, long-lasting condition must always be considered. In any event, the type of bisphosphonate, administration schedule, or both in patients with MGUS and bone loss would be different from the type and schedule in patients with multiple myeloma.5

Joan Bladé, M.D.
University of Barcelona, 08036 Barcelona, Spain
jblade@clinic.ub.es

Since publication of his article, Dr. Bladé reports receiving lecture fees and consulting fees from Novartis. No other potential conflict of interest relevant to this letter was reported.

5 References

1. 1

   Melton LJ III, Rajkumar SV, Khosla S, Achenbach SJ, Oberg AL, Kyle RA. Fracture risk in monoclonal gammopathy of undetermined significance. J Bone Miner Res 2004;19:25-30
   CrossRef | Web of Science | Medline

2. 2

   Pepe J, Petrucci MT, Nofroni I, et al. Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance. Br J Haematol 2006;134:485-490
   CrossRef | Web of Science | Medline

3. 3

   Politou M, Terpos E, Anagnostopoulos A, et al. Role of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin and macrophage protein 1-alpha (MIP-1a) in monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol 2004;126:686-689
   CrossRef | Web of Science | Medline

4. 4

   National Osteoporosis Foundation. Physician's guide to prevention and treatment of osteoporosis, Washington, DC: National Osteoporosis Foundation, 2003.
   

5. 5

   Lacy MQ, Dispenzieri A, Gertz MA, et al. Mayo Clinic consensus statement for the use of bisphosphonates in multiple myeloma. Mayo Clin Proc 2006;81:1047-1053
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Jessica Pepe, Maria Teresa Petrucci, Maria Lucia Mascia, Sara Piemonte, Valeria Fassino, Elisabetta Romagnoli, Salvatore Minisola. (2008) The Effects of Alendronate Treatment in Osteoporotic Patients Affected by Monoclonal Gammopathy of Undetermined Significance. Calcified Tissue International 82:6, 418-426
   CrossRef