The use of porous ceramics as bone graft substitutes (BGS) has been under consideration for over 30 years [1]. In particular calcium phosphates such as hydroxyapatite (HA) have been promoted as a result of their osteoconductive properties, i.e. that they stimulate bone apposition within their macroporous structures.

It is well established that both pore size [1] and pore connectivity [2] are critical morphological elements for a successful BGS. Thus biologically ‘optimal’ structures, with relatively large levels of porosity (> 70%) are consequently low in mechanical strength, with typical UCS values of between 1–8 MPa depending on the precise level of porosity and the pore size distribution. The aim of this investigation was to study the biological response to a porous HA with a relatively low level of macro-porosity (64%), but which possessed a highly interconnected micro-pore structure within the HA struts.

Phase pure porous HA implants were manufactured using a novel technique [3] with a mean macro-pore size of 230 ìm and a mean pore interconnection size of 110 μm. Cylindrical specimens 4.5 mm in diameter were implanted in the distal femur of 6 month New Zealand White rabbits and retrieved for histological and histomorphometric analysis at 4 weeks. The mineral apposition rate (MAR) was determined through the administration of fluorochrome labels at 1, 2 and 3 weeks.

After 4 weeks new bone had penetrated deep within the macro-pore structure and at high magnification osteocyte-like cells were observed occupying micro-pores within the ceramic struts. Furthermore, there was a significant increase in the MAR of bone formed within and surrounding the PHA (5.21 ìm.day-1, 4.42 ìm.day-1) as compared to the normal turnover rate of control bone (2.07 ìm.day-1, 2.09 ìm.day-1) during weeks 1-2 and 2–3, respectively.

The micro-porous network within the scaffold struts clearly influenced the host response. This could be linked to an associated increase in roughness or surface area, or it may reflect the greater level of strut permeability underlining the importance of nutrient transfer and the promotion of angiogenesis in scaffolds for bone repair.

To investigate the underlying mechanism of osteocyte death in osteonecrosis of the femoral head (ONFH).

Although there are a plethora of conditions that predispose to ONFH the underlying mechanism that results in the death of osteocytes is poorly understood. Consequently, treatment for early disease has a variable outcome. Recent investigation has focussed on the role of nitric oxide (NO) in the local control of bone turnover. NO is central to bone cell metabolism and has been implicated in the development of apoptosis.

Bone samples were harvested from the femoral heads of 40 patients undergoing total hip arthroplasty – 20 for advanced ONFH and 20 for osteoarthritis (control group). Immunocytochemical techniques were used to demonstrate evidence of NO synthase (iNOS and eNOS) as a marker of NO production and for evidence of apoptosis.

There was a marked increase in the expression of both eNOS and iNOS in the bone marrow and osteocytes from patients with ONFH secondary to steroids and alcohol with a correspondingly high proportion of apoptotic cells. Very little evidence of either eNOS or iNOS could be demonstrated in the control group and no significant apoptosis could be demonstrated. Samples from patients with ONFH secondary to sickle cell disease likewise had little evidence of apoptosis and a less marked increase iNOS production.

Our findings suggest that sickle cell disease may cause infarction of bone which subsequently leads to osteonecrosis. However, steroids and alcohol, or their metabolites, may have a direct cytotoxic effect upon bone leading to an increased NO production and NO-mediated apoptosis rather than necrosis. Our findings may provide important clues as to the underlying pathway leading osteocyte death. Therapeutic measures aimed at preventing production of toxic levels of NO or by blocking specific pathways in apoptosis may provide effective an treatment during the early stages of ONFH by halting disease progression.