Malignant transformation in patients with monoclonal gammopathy of undetermined significance treated with teriparatide for osteoporosis: a bicenter retrospective study and analysis of the French national pharmacovigilance database

Abstract Summary Malignant transformation in patients with monoclonal gammopathy of undetermined significance treated with teriparatide was evaluated. Among 29 patients, only two progressed to hematologic malignancy (one multiple myeloma, one Waldenström’s macroglobulinemia). These findings are reassuring and suggest that TPT may remain an option for selected patients with severe osteoporosis and MGUS. Purpose Osteoporosis is a highly prevalent bone disease with limited therapeutic options, particularly in multimorbid patients. Monoclonal gammopathy of undetermined significance (MGUS), a frequent finding in osteoporosis and a recognized fracture risk factor, often leads to contraindication of teriparatide (TPT), further restricting treatment choices. This study aimed to assess hematologic malignant transformation in osteoporotic patients with MGUS treated with TPT. Methods A retrospective bicenter observational study was conducted at Lille and Angers University Hospitals (2016–2022). Patients with osteoporosis and confirmed MGUS at TPT initiation were included. Demographic, hematologic, bone, and treatment parameters were collected. In parallel, hematologic malignancies reported with TPT were reviewed from the French national pharmacovigilance database (PVDB) over the same period. Results Twenty-nine patients (69% women; mean age 72.6 ± 12.6 years) were included. Most had major comorbidities (89.7% with Charlson Comorbidity Index ≥ 3). MGUS was IgG-type in 55.2% and IgM-type in 41.4%. The mean follow-up from TPT initiation was 60.2 ± 30.7 months (median 54.0; 95% CI 49.0–71.4). Two patients developed hematologic malignancy: one multiple myeloma (MM) 7 years after TPT and one Waldenström’s macroglobulinemia 21 months after initiation, both with intermediate-risk MGUS. TPT was well tolerated with premature discontinuation in 17.2% of cases. Of the two hematologic malignancies identified in the PVDB, only one (MM) occurred in a patient with pre-existing MGUS. Conclusion Malignant progression was rare, providing reassuring evidence regarding hematologic safety. TPT may be considered in selected patients with severe osteoporosis and MGUS, provided careful hematologic monitoring. Graphical abstract