New IOF position statement provides first clinical guidance on bone fragility in patients with MGUS

The International Osteoporosis Foundation (IOF) Committee of Scientific Advisors (CSA) Bone and Cancer Working Group published its position statement, "Clinical guidance on evaluation and management of bone fragility in patients with monoclonal gammopathy of undetermined significance (MGUS)", in Osteoporosis International on 8 September 2026. The statement reviews the available evidence on fracture risk and bone evaluation in MGUS and presents the first risk-adapted clinical practice algorithm for bone fragility in this patient group.

The authors describe bone fragility in MGUS as the combined result of three factors: classical osteoporosis risk factors, MGUS-related comorbidities such as neuropathy and impaired kidney function, and a direct effect of the abnormal plasma cells on bone that favours bone resorption. Evidence reviewed by the Working Group shows that patients with MGUS face roughly twice the risk of vertebral fracture and a 1.5-fold higher risk of hip fracture.

“MGUS is usually viewed through a haematological lens, with attention focused on its progression to myeloma. Yet evidence shows that these patients also face a substantially higher risk of fracture, particularly of the spine,” said Professor Cyrille B. Confavreux, Cancer Institute of Hospices Civils de Lyon and Université Claude Bernard Lyon 1, France, and lead corresponding author. “This position statement gives clinicians a pragmatic, risk-adapted pathway: screen for MGUS when investigating a fragility fracture, undertake a comprehensive bone evaluation when clinical MGUS is diagnosed, and treat patients at risk with antiresorptive agents at osteoporosis rather than oncology doses."

To help clinicians identify and manage patients at risk, the position statement offers the following recommendations:

• Inclusion of serum protein electrophoresis and serum free light chain measurement in the work-up for a fragility fracture.
• A comprehensive bone evaluation following a new diagnosis of clinical MGUS, corresponding to whenever an MGUS diagnosis has been made in patients with other diseases/events requiring investigation for paraprotein. The bone evaluation should cover fracture risk factors, comorbidities, bone turnover markers (at least a morning-fast serum CTX), and DXA at the hip and spine.
• Recognition of MGUS as a cause of secondary osteoporosis, alongside standard risk factors.
• A risk-adapted treatment strategy, with bisphosphonates as the preferred option.
• Annual follow-up for MGUS and a bone reassessment after three years, in the absence of any incident fragility fracture.

The guidance can support the wide range of clinicians who encounter patients with MGUS, including general practitioners, internists, geriatricians, endocrinologists, rheumatologists, haematologists, gynaecologists, and advanced practice nurses.

Professor Eugene McCloskey, Mellanby Centre for Musculoskeletal Research, University of Sheffield, UK, and Chair of the IOF CSA, highlighted what the guidance means for patients. “Although patients with MGUS are often supported by several specialists, their bone health can still be overlooked. By recognising MGUS as a cause of secondary osteoporosis, clinicians can identify patients at high risk earlier and offer treatment before a fracture occurs. While the evidence base will continue to evolve, this guidance can be implemented in clinical practice today.”

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Reference

Confavreux, C. B., Bouvard, B., et al., on behalf of the International Osteoporosis Foundation (IOF) Committee of Scientific Advisors Bone and Cancer Working Group (2026). Clinical guidance on evaluation and management of bone fragility in patients with monoclonal gammopathy of undetermined significance (MGUS): an IOF position statement. Osteoporosis International. https://doi.org/10.1007/s00198-026-08178-0

About IOF

The International Osteoporosis Foundation (IOF) is the world’s largest non-governmental organisation dedicated to the prevention, diagnosis, and treatment of osteoporosis and related musculoskeletal diseases. Its members — including committees of leading scientific researchers and 349 patient, medical, and research organisations across 152 countries — work together to make fracture prevention and healthy mobility a global healthcare priority.

www.osteoporosis.foundation @iofbonehealth