From the Guidelines
Yes, multiple myeloma does cause lytic bone lesions, which are a hallmark feature of the disease, occurring in approximately 85% of patients, as reported in the most recent study 1. These lesions appear as "punched-out" areas on X-rays and are caused by the imbalance between bone resorption and bone formation, leading to increased bone destruction. The bone destruction happens because myeloma cells produce factors that activate osteoclasts (bone-destroying cells) while simultaneously inhibiting osteoblasts (bone-forming cells) 1. The most commonly affected areas include the spine, skull, pelvis, ribs, and proximal long bones. These lytic lesions can cause significant complications including:
- Bone pain
- Pathological fractures
- Spinal cord compression
- Hypercalcemia The presence of lytic bone lesions is one of the CRAB criteria (hypercalcemia, renal failure, anemia, bone lesions) used to diagnose symptomatic myeloma requiring treatment 1. Management typically includes anti-myeloma therapy along with bone-targeted agents such as:
- Bisphosphonates (zoledronic acid 4mg IV monthly)
- Denosumab (120mg subcutaneously monthly) to reduce skeletal-related events, as recommended by the NCCN Guidelines for MM 1. It is also recommended to continue bone-targeting treatment for up to 2 years and beyond 2 years based on clinical judgement, with the frequency of dosing depending on individual patient criteria and response to therapy 1.
From the Research
Myeloma and Lytic Bone Lesions
- Myeloma is characterized by enhanced bone loss, commonly associated with diffuse osteopenia, focal lytic lesions, pathologic fractures, hypercalcemia, and bony pain 2.
- Bone disease in multiple myeloma is characterized by lytic bone lesions, which can cause severe bone pain, pathologic fractures, and hypercalcemia 3.
- The lytic bone disease in myeloma differs from that in other cancer patients who have lytic bone metastases, with increased osteoclastic bone destruction and suppressed or absent osteoblast activity 3.
Pathogenesis of Myeloma Bone Disease
- The imbalance between bone regeneration and bone resorption underlies the pathogenesis of osteolytic bone disease, with increased osteoclast proliferation and activity accompanied by inhibition of bone-forming osteoblasts leading to progressive bone loss and lytic lesions 4.
- A major unbalanced bone remodeling (increased bone resorption with normal to low bone formation) is the characteristic feature of patients presenting lytic bone lesions 5.
- The interactions between myeloma cells and the tumor-bone microenvironment contribute to the bone disease and continued myeloma progression 4.
Treatment and Management
- Bisphosphonates are specific inhibitors of osteoclastic activity and have been evaluated in patients with myeloma with bone disease, reducing skeletal complications and improving quality of life 2.
- Novel agents targeting bone disease are under investigation, with the goal of preventing bone loss and improving bone quality, as well as harnessing myeloma tumor growth 4.
- Bone anabolics, which stimulate osteoblasts, are a potential new therapeutic option for myeloma-induced bone disease, with preclinical applications demonstrating positive outcomes for bone repair and fracture resistance 6.