Sex dependent regulation of osteoblast response to implant surface properties by systemic hormones

BACKGROUND: Osseointegration depends on the implant surface, bone quality and the local and systemic host environment, which can differ in male and female patients. This study was undertaken in order to determine if male and female cells respond differently to titanium surfaces that have micron-scale roughness and if interactions of calciotropic hormones [1α,25(OH)(2)D(3 )and 17β-oestradiol (E(2))] and microstructured surfaces on osteoblasts are sex dependent. METHODS: Osteoblasts from 6-week old Sprague-Dawley rats were cultured on tissue culture polystyrene (TCPS) or on titanium (Ti) disks with two different surface topographies, a smooth pretreated (PT) surface and a coarse grit-blasted/acid-etched (SLA) surface, and treated with 1α,25(OH)(2)D(3), E(2), or E(2 )conjugated to bovine serum albumin (E(2)-BSA). RESULTS: Male and female cells responded similarly to Ti microstructure with respect to cell number and levels of osteocalcin, transforming growth factor-β1, osteoprotegerin and prostaglandin E(2 )in their conditioned media, exhibiting a more differentiated phenotype on SLA than on PT or TCPS. E(2 )and E(2)-BSA increased differentiation and local factor production, an effect that was microstructure dependent and found only in female osteoblasts. 1α,25(OH)(2)D(3 )increased osteoblast differentiation and local factor production in female and male cells, but the effect was more robust in male cells. CONCLUSIONS: Male and female rat osteoblasts respond similarly to surface microstructure but exhibit sexual dimorphism in substrate-dependent responses to systemic hormones. Oestrogen affected only female cells while 1α,25(OH)(2)D(3 )had a greater effect on male cells. These results suggest that successful osseointegration in males and females may depend on the implant surface design and correct levels of calciotropic hormones.