Supporting data for \"Vertebral fractures in multiple myeloma show mesenchymal stromal cell recruitment, osteoblast activation, and early sclerotic bone healing but hampered mature healing\"

Vertebral fractures are common in multiple myeloma (MM) as part of the myeloma associated bone disease with increased osteolytic activity and inhibited osteoblastic activity. It remains unclear whether vertebral fractures can overcome osteoblast inhibition and sustain healing in fractures. We analyzed vertebral fracture biopsies and paired iliac crest samples from 38 MM patients, and fracture biopsies from 12 osteoporosis patients using histomorphometry, ex vivo MSC culture, and bulk and single-cell transcriptomics. Although highly heterogenic many MM fractures displayed substantial formation of sclerotic bone, often exceeding that of osteoporosis patients. Fractures showed MSC enrichment and activated osteoblasts in MM, despite an inflamed and immunosuppressive microenvironment expressing osteoblast-inhibitory signals. However, despite initial repair, persistence of immature bone in late-stage fractures and reduced osteogeneic potential of MSCs suggest that remodeling of immature bone to lamellar structured bone might be delayed or impaired in MM with implications for bone quality and fracture stability.