1st line combination treatment with proteasome-inhibitor and zoledronic acid is effective in reducing later fractures in multiple myeloma irrespective of MM bone disease

Introduciton We examined the medical records of 344 multiple myeloma (MM) patients treated with autologous stem cell transplantation in Oulu University Hospital in 1996-2020. Methods Median age of the patients was 61 years and 54.9% were males. ISS was available for 58.4%, R-ISS for 35.9% and IMWG status for 39.4% of the patients. A total of 72.1% had myeloma-associated bone disease and 47.9% had fracture/s at the time of diagnosis. Altogether 58.3% of the patients received proteasome-inhibitor containing treatment at 1st line. Treatment for MM bone disease was given to 90.8% of the patients, 49.4% received zoledronic acid and 29.6% pamindronate. A total of 28.7% of the patients suffered from later fracture. Median follow-up time in this study was 50 months (1-339). Results MM bone disease at diagnosis was associated with inferior overall survival (p=0.004) as well as with fracture at diagnosis (p=0.005) irrespective of the type of fracture (pathological vs osteoporotic). The site of the fracture showed statistical significance in that fractures in vertebrae or ribs were associated with better outcome (p=0.028). There were fewer later fractures in patients treated with zoledronic acid although this association did not reach statistical significance (p=0.058). This tendency was clearer in patients with no MM bone disease at diagnosis (p=0.049). The best combination treatment to prevent later fractures was the combination of proteasome-inhibitor and zoledronic acid (p=0.019). Conclusions This study suggests that the best treatment option to prevent later fractures might be proteasome-inhibitor combined with zoledronic acid.