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Research Topics

Our main research area is bone pathology, including cancer-induced bone disease, and glucocorticoid- and menopausal-induced osteoporosis.   

Most bone pathologies result from disregulation of bone remodeling, a process consisting in removal of “old bone” by osteoclasts and formation of “new bone” by osteoblasts. Bone remodeling is classically investigated at the cellular/molecular level and at the systemic level. In contrast, research at KCB focuses on an intermediate level of complexity: on the supracellular organization of the bone remodeling site, i.e. the micoenvironment where the many diverse signals regulating bone remodeling are integrated. Different projects are ongoing.

  • The bone remodelling compartment (BRC)

BRCs are microanatomic structures associated with bone remodelling sites that are overlooked in classical histomorphometry. Our systematic search in different pathophysiological conditions showed an association between the occurrence of BRCs and bone formation activity. This association suggests a role of BRCs in bone formation. This role is now being investigated in relation with different aspects. These include the role of the BRCs in osteoblast recruitment; the role of the BRC canopy as a “marrow-bone barrier” controlling the levels of ions and cytokines, as well as the migration of cells (for example preventing contacts of cancer cells with bone surface cells); its role in communicating with the capillary network that we found interacting with the BRC canopies; its role in interacting with monocytes apparently positioned along the BRC canopy; …

  • The reversal cells

The reversal cells are the cells colonizing resorption lacunae vacated by osteoclasts after resorption. Although they appear as the natural agents “coupling” bone resorption and formation, they are overlooked in bone research, incl histomorphometry. We found that they are osteoblast lineage cells involved in preparing the bone surface for bone formation, and that malfunction of reversal cells contributes to lack of bone formation in osteoporosis. Therefore, we are currently investigating further the role of these reversal cells both under physiological and pathological conditions (incl. myeloma)

  • Osteoclastic bone resorption

According to the common belief of bone scientists osteoclasts resorb bone like a “drilling machine” making pits. However, we have discovered that this cannot be the whole truth. We have found that osteoclasts also resorb bone like a “bulldozer” generating long and deep cavities, trenches. Our work has shown that these reflect two different resorption modes and are differently sensitive to drug treatment.

We have a number projects running which by different means aim at characterizing the pit- and trench-mode, such as:

  • Analyzing the resorptive behavior of osteoclasts by time-lapse distinguishing between pit- and trench-mode and characterizing their sensitivity to various inhibitors in real-time.
  • Understanding the molecular and structural requirements allowing osteoclasts to switch between pit- and trench-mode.

In addition we also use our specialized knowledge on osteoclastic bone resorption to understand important clinical problems such as:

  • Understanding the molecular and cellular causes for the enhanced bone loss observed in osteoporosis patients receiving a low dose of the cathepsin K inhibitor, odanacatib.
  • Understanding why zoledronic acid shows a highly variable potency from one cancer patient to the other. 
  • Osteoclast fusion

Cell fusion resulting in a multinucleated cell is an essential step in osteoclast differentiation. This fusion process is poorly understood and has classically been considered to be a process where osteoclasts fuse more or less at random. However, we have shown in a series of publications that osteoclasts carefully choose their fusion partner based on differences between the two fusion partners.
Our recent research suggests that this careful selection of fusion partner and the involvement of different fusion factors at different stages of nuclearity may be a way to control whether more or larger osteoclasts are formed under physiological conditions.
We have a continued interest in understanding this selective fusion of osteoclasts and how this may be the key to understand where, how many and how large osteoclasts form at a given bone site.

  • Diagnostic and prognostic use of bone turnover markers in breast cancer and prostate cancer patients with bone metastases 

We see it as one of our important tasks to transfer the knowledge obtained from basic research into the clinical relevant setting. In this context our specialized knowledge about bone cells are of direct clinical relevance when it comes to diagnosis, monitoring and treatment of cancer patients with metastases to bone. Specific examples are mentioned below for two clinical trials we have initiated:

  • In 2016 we initiated a clinical trial, which recruits 50 breast cancer patients with newly identified bone metastases and who starts up treatment with either bisphosphonate or denosumab. We follow these patients for up to 3 years and determine the levels of a bone resorption marker (CTX) and a bone formation marker (PINP) in order to evaluate their diagnostic and prognostic value. This project is carried out at Lillebaelt Hospital and Hospital of South West Jutland.
  • In 2017 we will initiate a clinical trial recruiting prostate cancer patients both without and with bone metastases and follow them for a period of up to 3 years and determine the levels of CTX and PINP in order to evaluate their diagnostic and prognostic value. It is planned that the study in total will enroll around 400 prostate cancer patients at Lillebaelt Hospital.

Senest fagligt revideret: 13-10-2016

Siden er sidst opdateret 13-10-2016.
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