Abstract
Bone metabolism has not been systematically studied in primary (AL) amyloidosis. Thus we prospectively evaluated bone remodeling indices in 102 patients with newly diagnosed AL amyloidosis, 35 healthy controls, 35 newly diagnosed myeloma and 40 monoclonal gammopathy of undetermined significance patients. Bone resorption markers (C-telopeptide of type-1 collagen, N-telopeptide of type-1 collagen) and osteoclast regulators (soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG)) were increased in AL patients compared with controls (P<0.01), but bone formation was unaffected. Myeloma patients had increased bone resorption and decreased bone formation compared with AL patients, while sRANKL/OPG ratio was markedly decreased in AL, due to elevated OPG in AL (P<0.001). OPG correlated with N-terminal pro-brain natriuretic peptide (P<0.001) and was higher in patients with cardiac involvement (P=0.028) and advanced Mayo stage (P=0.001). OPG levels above the upper value of healthy controls was associated with shorter survival (34 versus 91 months; P=0.026), while AL patients with OPG levels in the top quartile had very short survival (12 versus 58 months; P=0.024). In Mayo stage 1 disease, OPG identified patients with poor survival (12 versus >60 months; P=0.012). We conclude that increased OPG in AL is not only a compensation to osteoclast activation but may also reflect early cardiac damage and may identify patients at increased risk of death within those with earlier Mayo stage.
Highlights
Primary systemic (AL) amyloidosis is a rare disease characterized by deposits of monoclonal immunoglobulin light chain-derived amyloid fibrils in vital organs
Deregulation of bone metabolism is common in plasma cell dyscrasias, including multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS),[3,4,5] but very little is known for bone remodeling in patients with AL
The presence of a plasma cell clone in the unique microenvironment of the bone marrow causes multiple organ dysfunction through the production of the amyloidogenic light chains, while within the bone marrow microenvironment the plasma cells interact with either cellular or non-cellular components of the bone, but no data exist about this interaction
Summary
Primary systemic (AL) amyloidosis is a rare disease characterized by deposits of monoclonal immunoglobulin light chain-derived amyloid fibrils in vital organs. Widespread deposition of amyloid fibrils causes multisystem organ dysfunction.[1] Kidneys, heart, liver, nerves, gastrointestinal tract and soft tissues are most commonly involved.[2] Deregulation of bone metabolism is common in plasma cell dyscrasias, including multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS),[3,4,5] but very little is known for bone remodeling in patients with AL amyloidosis. Bone manifestations are considered to be rare in AL patients and include mainly vertebral amyloidomas, characteristic circumscribed osteolytic lesions due to amyloid deposits and chronic arthropathies.[6,7,8,9] In the largest published series, Schonland et al.[10] identified four cases among 330 AL patients with osteolytic lesions in the absence of MM. The aim of our prospective study was to evaluate bone metabolism in newly diagnosed patients with AL amyloidosis, to compare the results with those of patients with other plasma cell neoplasms, including MM and MGUS, and explore possible correlations with disease characteristics, including survival
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