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Altered cortical microarchitecture in patients with monoclonal gammopathy of undetermined significance.

ABSTRACT: Patients with monoclonal gammopathy of undetermined significance (MGUS) are at increased fracture risk, and we have previously shown that MGUS patients have altered trabecular bone microarchitecture compared with controls. However, there are no data on whether the porosity of cortical bone, which may play a greater role in bone strength and the occurrence of fractures, is increased in MGUS. Thus, we studied cortical porosity and bone strength (apparent modulus) using high-resolution peripheral quantitative computed tomography imaging of the distal radius in 50 MGUS patients and 100 age-, gender-, and body mass index-matched controls. Compared with controls, MGUS patients had both significantly higher cortical porosity (+16.8%; P < .05) and lower apparent modulus (-8.9%; P < .05). Despite their larger radial bone size, MGUS patients have significantly increased cortical bone porosity and reduced bone strength relative to controls. This increased cortical porosity may explain the increased fracture risk seen in MGUS patients.

SUBMITTER: Farr JN

PROVIDER: S-EPMC3907752 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Altered cortical microarchitecture in patients with monoclonal gammopathy of undetermined significance.

Farr Joshua N JN Zhang Wei W Kumar Shaji K SK Jacques Richard M RM Ng Alvin C AC McCready Louise K LK Rajkumar S Vincent SV Drake Matthew T MT

Blood 20131113 5

Patients with monoclonal gammopathy of undetermined significance (MGUS) are at increased fracture risk, and we have previously shown that MGUS patients have altered trabecular bone microarchitecture compared with controls. However, there are no data on whether the porosity of cortical bone, which may play a greater role in bone strength and the occurrence of fractures, is increased in MGUS. Thus, we studied cortical porosity and bone strength (apparent modulus) using high-resolution peripheral q ...[more]

PMID: 24227822

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Project description:We analyzed MYD88 and CXCR4 mutation status of 260 patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance using allele-specific real time quantitative polymerase chain reaction and Sanger sequencing, respectively. A subgroup of 119 patients was further studied with next-generation sequencing of 11 target genes (MYD88, CXCR4, ARID1A, KMT2D, NOTCH2, TP53, PRDM1, CD79B, TRAF3, MYBBP1A, and TNFAIP3). MYD88 (L265P) was found at diagnosis in 91% of patients with Waldenström macroglobulinemia and in 60% of patients with IgM monoclonal gammopathy of undetermined significance using allele-specific polymerase chain reaction analysis. MYD88 mutations other than the classical L265P (V217F, S219C and M232T) were found in four cases by next-generation sequencing. Waldenström macroglobulinemia patients with wild-type MYD88 had a distinct clinical phenotype characterized by less bone marrow infiltration (P=0.01) and more frequent extramedullary involvement (P=0.001) compared to patients with mutated MYD88 Patients with wild-type MYD88 did not show additional mutations in the other target genes. CXCR4 mutations were found by Sanger sequencing in 22% of patients with Waldenström macroglobulinemia. With next-generation sequencing, a CXCR4 mutation was detected in 23% of patients with Waldenström macroglobulinemia and 9% of those with IgM monoclonal gammopathy of undetermined significance. Asymptomatic Waldenström macroglobulinemia patients harboring a CXCR4 mutation had a shorter treatment-free survival (51 months) than that of patients with wild-type CXCR4 (median not reached) (P=0.007). Analysis of variant allele frequencies indicated that CXCR4 mutations were present in the dominant clone in the majority of cases. Recurrent somatic mutations of KMT2D were found in 24% of patients with Waldenström macroglobulinemia and 5% of patients with IgM monoclonal gammopathy of undetermined significance and were primarily subclonal.

Dataset Information

Altered cortical microarchitecture in patients with monoclonal gammopathy of undetermined significance.

Publications

Altered cortical microarchitecture in patients with monoclonal gammopathy of undetermined significance.

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