Biological aspects of synovial fluid mediated aseptic prosthesis loosening

Aseptic prosthesis loosening is the most common reason for late failure of total hip arthroplasties. Resorption of the peri-prosthetic bone, resulting in a loose prosthesis is characteristic for aseptic loosening. The integrity of the bone tissue around the prosthetic components is dependent on bone forming osteoblasts and bone degrading osteoclasts. Synovial fluid (SF) is present in the vicinity of the bone tissue surrounding the prosthetic joint and may thus be important for periarticular bone turnover. In this thesis, SF from patients with aseptic loosening was studied regarding its effect on: osteoblast proliferation, osteoblast differentiation, osteoblast matrix synthesis and bone resorption. The IGF-sytem in patients with aseptic loosening was also investigated. Generally, SF from patients with osteoarthritis was used for comparison, but also SF from healthy subjects in the bone resorption experiments. SF from patients with aseptic loosening reduced cell proliferation in human osteoblasts compared to SF from patients with osteoarthritis. This difference was dependent on lower levels of insulin-like growth factor I (IGF-I) in the synovial fluid from the aseptic loosening patients, who also had lower and even sub-normal serum levels of IGF-I compared to the osteoarthritis patients. These data suggest that a relative lack of IGF-I in synovial fluid, possibly dependent on low serum IGF-I levels, may play a role in aseptic prosthesis loosening. Procollagen I mRNA in osteoblasts decreased after exposure to either SF from patients with aseptic loosening or osteoarthritis, whereas osteocalcin expression increased in mouse calvarias in response to both types of SF. Alkaline phosphatase expression in mouse calvarias increased after treatment with SF from patients with osteoarthritis, but not in response to aseptic loosening SF. Total protein synthesis in osteoblasts increased after exposure to both types of SF. Procollagen 1 carboxyterminal propeptide (PICP), a marker of collagen synthesis increased after treatment with aseptic loosening SF, but not in response to osteoarthritis SF. These findings imply that matrix synthesis and osteoblast differentiation may be increased in aseptic prosthesis loosening, even if there is a net loss of bone, presumably dire to an even higher increase in bone resorption. Bone resorption in mouse calvariae was induced equally by both aseptic loosening and osteoarthritis S17s, but not after treatment with SF from normal subjects. Aseptic loosening and osteoarthritis SFs had different effects on OPG, RANK and RANKL expression, which implies that the mechanism of activation of bone resorption is different between these two types of SFs. Anti-serum towards IL-1 alfa, IL-1 beta, TNF-alfa, IL-17 and soluble IL-6 receptor inhibited the stimulating effect on bone resorption, induced by aseptic loosening or osteoarthritis SF from some patients, but there was no general pattern among the two types of SF. This illustrates that there is a high degree of variability between different patients in terms of the mechanisms that activate bone resorption. In conclusion, SF has a wide range of effects on bone metabolism. SF may act as mediator for aseptic prosthesis loosening