Histomorphometric and microarchitectural analyses using the 2 mm bone marrow trephine in metastatic breast cancer patients-preliminary results

Abstract

Background: Bone-targeted agents are widely used for the treatment of osteoporosis, the prevention of cancer-therapy induced bone loss, and for reducing the risk of skeletal related events in patients with metastatic disease. Despite widespread use, relatively little is known about the in vivo effect of these agents on bone homeostasis, bone quality, and bone architecture in humans. Traditionally bone quality has been assessed using a transiliac bone biopsy with a 7 mm "Bordier" core needle. We examined the possibility of using a 2 mm "Jamshidi" core needle as a more practical and less invasive method to assess bone turnover and potentially other tumor effects.

Methods: A pilot study on the feasibility of assessing bone quality and microarchitecture and tumor invasion using a 2 mm bone marrow trephine was conducted. Patients underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for bone microarchitecture, bone density, and histomorphometry. The study plan was to accrue three patients with advanced breast cancer to assess the feasibility of the study before enrolling more patients.

Results: The procedure was well tolerated. The sample quality was excellent to analyze bone trabecular microarchitecture using both microCT and histomorphometry. Intense osteoclastic activity was observed in a patient with extensive tumor burden in bone despite intravenous bisphosphonate therapy.

Discussion: Given the success of this study for assessing bone microarchitecture, bone density, and histomorphometry assessment using a 2 mm needle the study will be expanded beyond these initial three patients for longitudinal assessment of bone-targeted therapy.

Keywords: Bisphosphonate; Breast cancer; Histomorphometry; MicroCT; Microarchitecture.

Fig. 1

MicroCT images, for patient #1, #2, and #3.

Fig. 2

Histological and histomorphometric analysis of bone. Hematoxyline and Eosin (HE), von Kossa and van Gieson (VKVG), and tartrate-resistant acid phosphatase (TRAP) staining of plastic sections of bone samples from three patients. HE stain shows the presence of tumor (T) in patient #2. Patient #1 and #2 shows the presence of osteoid volume (O) by VKVG stain (middle panel). No osteoclast is seen in the field shown for sample of patient #1. BM: bone marrow and MB: mineralized bone. Among the microscopic field presented only sample from patient #2 show the presence of osteoclasts (C) by TRAP stain (right panel). Osteoblasts were stained with toludine blue.