Clinical guidance on evaluation and management of bone fragility in patients with monoclonal gammopathy of undetermined significance (MGUS): an IOF position statement

Summary: Monoclonal gammopathy of undetermined significance (MGUS) is a frequent hematological condition that occurs in later life. MGUS is associated with increased fragility fractures that mix individual osteoporotic risk factors, MGUS-related comorbidities, and direct MGUS bone impact such as senescence of plasma cells. This International Osteoporosis Foundation (IOF) position statement aims at evaluating the potential relationship between MGUS and fracture risk, as well as methods for evaluating bone involvement in MGUS. Finally, we propose the first bone clinical guidance for patients with MGUS to improve their bone health. Background: Monoclonal gammopathy of undetermined significance is a prevalent hematological condition in adults, characterized by the presence of an abnormal monoclonal protein in the blood without concomitant symptoms or malignancy. MGUS is of considerable bone significance and contributes to fragility fractures in adults. Methods: In this review, data pertaining to bone fragility were collected, including epidemiological fracture data in patients with MGUS, bone mineral density (BMD), bone microarchitecture, bone turnover marker, and bone histomorphometry data. Results: Collectively, these findings suggest an elevated risk of fractures, especially in presence of osteoporotic risk factors or comorbidities, and a diminished BMD due to augmented bone resorption. Studies focusing on the treatment of this condition are limited. Conclusion: Based on this analysis, we present the International Osteoporosis Foundation (IOF) position statement for bone evaluation and management of these patients. We recommend a risk-adapted treatment strategy. A proposal of bone clinical guidance dedicated to patients with MGUS is presented, suggesting bisphosphonates as the preferred treatment option.