Review Question - QID 211475

This patient has multiple myeloma, which affects bone turnover by both increasing osteoclastogenesis and down regulating osteoblast function.

Multiple myeloma (MM) is one of the most common primary bone malignancies and is seen in patients mostly over the age of 40. MM is caused by neoplastic plasma cell proliferation, causing overproduction of immunoglobulins. These malignant cells affect bone turnover in multiple ways. First, several factors function, including RANK-L, M-CSF, IL-6, and IL-11, to promote osteoclastic function, creating bone breakdown. Additionally, tumor necrosis factor (TNF) and Dickkopf-1 (DKK-1) down regulate osteoblast proliferation and function. New therapies are being produced to target these factors in order to modulate bone turnover in MM patients.

Longo et al. reviewed an approach to treating myeloma bone disease, noting that the bony manifestations of MM play an important role in a patient's survival. They note that bisphosphonates have long been used with success in decreasing associated bony events, but new, targeted therapies were being investigated. They specifically review therapies that target inhibitors of osteoblast differentiation including TNF and DKK-1.

Weber et al. wrote an instructional course lecture on malignant bone tumors, noting that many of these patients complain of pain at rest or at night. They stress the importance of early diagnosis in order to promote staging and treatment. After detailing management strategies relating to different tumors, they close by recommending that these patients be under close surveillance by a multidisciplinary team in order to provide the best outcomes.

Figure A demonstrates an AP radiograph of a left femur showing multiple lytic lesions representative of multiple myeloma.

Incorrect Answers:
Answer 1: DKK-1 is responsible to for down regulating osteoblast function, not promoting osteoclast function.
Answer 3: Osteoprotegerin synthesis is down regulated, leading to a higher degree of osteoclast activation than normal.
Answer 4: IL-6 and IL-11 both up regulate osteoclast function in MM, leading to more bone turnover and breakdown.
Answer 5: In cases of suspected MM, skeletal survey should be ordered as bone scans are "cold" in 30% of cases due to the lack of associated osteoblastic activity.