Bone recovery after treatment study: Evidence of myeloma bone disease repair and partial microenvironment recovery

Myeloma bone disease (MBD) affects ~90% of myeloma patients, causing pain and reduced quality of life. Current anti-resorptive treatments retard further destruction but do not repair bone. As new myeloma therapies emerge, understanding their impact on MBD is crucial. This pilot study assessed the feasibility of longitudinally measuring bone recovery in newly diagnosed myeloma patients receiving first-line therapy (e.g. induction ± autologous stem cell transplant, plus zoledronic acid), as a prelude to formally assessing bone anabolic strategies. Patients underwent whole-body low-dose computed tomography imaging and bone marrow biopsy at baseline and 3 months post-induction/autograft, alongside monthly bone turnover markers. All patients had evidence of partial osteolytic lesion repair, with one patient having resolution of some lesions. Trephine analysis revealed increased trabecular bone volume (p = 0.003) and osteoblast number (p < 0.05). However, osteocyte canalicular coverage was significantly reduced (p < 0.01). Serum C‑terminal telopeptide of type I collagen was suppressed from 2 months (p < 0.0001), and sclerostin from 3 months (p = 0.011). This pilot confirms the study design to be feasible. Results suggest that osteolytic lesions have the potential for partial repair, possibly supported by proteasome inhibitors. However, bone lesion resolution is rare, potentially impaired by poor lacunar network connectivity. These data highlight the ongoing need for novel, bone-targeted therapies to support MBD recovery.