Rationale:​ While treatment strategies for multiple myeloma have evolved radically over the last decades, little is known about the risk of fractures for symptomatic multiple myeloma patients over time.

Objective:​ To determine the effect of different treatment periods (1996–2000, 2001–2006 and 2007–2011) on the risk of fractures in patients with multiple myeloma.

Methods:​ This retrospective case-control study included patients with multiple myeloma in Denmark, using the Danish National Health Service. Cases were defined as patients who had sustained a fracture between 1996 and 2011, and controls were those without a fracture. Exposure was defined as an ICD code for multiple myeloma. Vertebral fractures, gender, and age were considered in secondary analyses. Conditional logistic regression was used to estimate odd ratios (ORs) of fracture risk, and the analyses were adjusted for comorbidities and recent drug use.

Results:​ The study population consisted of 925,341 cases, and the same number of matched controls, of whom 1334 patients with multiple myeloma. Among cases, the risk of any fracture was higher in multiple myeloma patients compared to patients without multiple myeloma (any fracture:​ ORadj[95% CI] 1996–2000:​ 1.7[1.3–2.3];​ 2001–2006:​ 1.3[1.1–1.6];​ 2007–2011:​ 1.7[1.4–2.2]). Although fractures were mainly non-vertebral, the risk of vertebral fractures in particular was higher in multiple myeloma patients (vertebral fracture:​ ORadj[95% CI] 1996–2000:​ 3.5[1.4–8.6];​ 2001–2006:​ 4.0[1.9–8.2];​ 2007–2011:​ 3.0[1.6–5.7]).

Conclusions:​ Despite new treatment strategies and improved supportive care, this study showed no decreased fracture risk for multiple myeloma patients over time. New treatment strategies, even if they have a positive impact on overall survival, offer no guarantee for a corresponding reduction in bone lesions.