Fracture risk in patients with monoclonal gammopathy of undetermined significance.
ABSTRACT Little information is available on the risk of fractures in patients with monoclonal gammopathy of undetermined significance (MGUS). We identified 1535 patients with MGUS between 1978 and 2003 in North Jutland County, Denmark. The population control group consisted of 15 350 persons selected from the Danish Central Population Registry, matched by age and sex. Data on fractures in the two groups were obtained from the regional Hospital Discharge Registry. In the MGUS cohort, 187 first-time fractures were identified during 9754 person-years of follow-up, corresponding to an incidence rate of 19/1000 person-years. The adjusted relative risk for fractures among MGUS patients compared with population controls was 1.4 [95% confidence interval (CI), 1.2-1.6]. After 5 years of follow-up, the risk difference was 1.8% (95% CI, 0.5-3.0). Six of the 187 MGUS patients with fractures were later diagnosed with malignant transformation. Relative risks for fractures were increased in IgG-type MGUS [1.3 (95% CI,1.1-1.6)], IgM-type MGUS [1.6 (95% CI, 1.1-2.2)] and MGUS with kappa light chain [1.4 (95% CI, 1.1-1.7)]. MGUS patients had an increased risk of fractures, which could not be explained by comorbidity, advanced age, gender or malignant transformation.
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ABSTRACT: Considering the special relation of human multiple myeloma (MM) to bones, it is of importance to clarify the early steps of bone involvement in this disease. In this work, using bone histomorphometry (including histoenzymologic and kinetic studies for the first time), we have evaluated the bone remodeling (i.e., bone resorption and bone formation rates) of 16 individuals with early MM in comparison with that of 10 with benign monoclonal gammopathy (BMG) and that of 17 patients with previously untreated overt MM. A significantly increased osteoblastic recruitment was observed in the individuals with early MM when compared with those with BMG (P less than 0.01). A significant (P less than 0.01) increased bone resorption (i.e., eroded surfaces, osteoclast numbers and surfaces) was observed from the early stage of MM in comparison with the BMG status where bone resorption remained within the normal range. At the tissue level, there was no difference in terms of bone resorption between early and overt MM. On the other hand, osteoblast activity was significantly reduced in patients with overt MM (P less than 0.05 by comparison with those with early MM). A significant enhancement of osteoblastic recruitment with an increased generation of new osteoclasts is an early critical event in the pathogenesis of human MM. Of particular importance is the early stimulation of osteoblasts, since these cells produce high amounts of IL-6, a potent myeloma cell growth factor and a critical cytokine for the formation of osteoclasts in the bone marrow.Journal of Clinical Investigation 08/1991; 88(1):62-6. · 12.81 Impact Factor
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ABSTRACT: To determine if excessive osteoclastic-mediated bone resorption (BR) is an early tumor-induced event in multiple myeloma (MM), BR was assessed at first presentation on quantitative bone biopsy in 87 individuals evaluated for monoclonal gammopathy of undetermined significance (MGUS) and reinterpreted according to the presenting features and subsequent follow-up evaluation. As a reference population, 48 patients with previously untreated overt MM were evaluated under similar conditions. The median level of BR was significantly higher in 48 overt MM versus 87 MGUS patients (12.2% v 5.1% [normal level, <6%], P <.01). Actually, 93% of overt MM patients had an excessive BR versus 45% of MGUS patients at presentation (P <.01) According to simple presenting parameters (> or <5% plasma cells within the bone marrow, presence or absence of mild anemia/neutropenia), 31 individuals were classified as low-risk MGUS, 32 high-risk MGUS, and 24 indolent MM. An excessive BR was observed in 16% of low-risk MGUS, 46% of high-risk MGUS (P <.01 v low-risk MGUS), 79% of indolent MM (P <.05 v high-risk MGUS), and 93% of overt MM patients. Of major interest, the level of BR in indolent MM (11.2%) was identical to that in overt MM (12.2%) but significantly higher than in both low-risk (4%, P <.01) and high-risk (5.6%, P <.01) MGUS. When considering the follow-up evaluation of MGUS patients, an excessive BR at presentation was observed in 52% of MGUS cases that turned out to be unstable or developed subsequent MM, but in only 4% of stable MGUS (P <.01). More precisely the level of BR of low-risk MGUS that either turned out to be unstable or that developed into MM was significantly higher at presentation than that of subsequent stable MGUS (4.4% v 2.9%, P <.05). The same difference was observed in both high-risk MGUS and indolent MM according to subsequent follow-up studies (8.1% v 3.4% and 11.7% v 6%, respectively, P <.05). Of major interest, the level of BR in 11 stable high-risk MGUS cases actually fulfilling the diagnostic criteria of smoldering MM was very low (3.4%) and similar to that in stable low-risk MGUS (2.9%). We conclude that a quantifiable excess of BR in MGUS is significantly associated with progression and thus is an early symptom of malignancy in these individuals.Blood 07/1996; 87(11):4762-9. · 9.06 Impact Factor
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ABSTRACT: The Danish Cancer Registry is a population-based registry containing data on the incidence of cancer throughout Denmark since 1943. Reporting of cancer was made mandatory by administrative order in 1987. Details of individual cases of cancer are available according to the 7th revision of the International Classification of Diseases (ICD) for all years, and according to the ICD-O since 1978. A core data set is kept on each individual which includes date of birth, sex, date of cancer diagnosis, method of verification, date of death and cause of death. This paper describes the history of the registry, its data sources and its procedures, including quality control and access to data. Integration of both research activities and registration since the inception of the Registry has maintained the completeness and validity of the data for 1943-1996.Danish medical bulletin 12/1997; 44(5):535-9. · 0.92 Impact Factor