Osteolysis significance

Metastatic bone disease (MBD) is characterized by very high levels of bone turnover in regions proximal to the tumour [33]. Bone resorption inhibitors such as bisphosphonates represent the current standard of care for the treatment of bone metastases primarily due to breast or prostate cancer and multiple myeloma. It has been proposed that other strong anti-resorptives such as a Cat K inhibitor could be useful in the treatment of bone metastases. Evidence for this has been presented in the form of a preclinical MBD model in which human breast cancer cells are implanted into nude mice. Treatment with a Cat K inhibitor gave a significantly lower area of breast cancer-mediated osteolytic lesions in the tibia [34]. In a separate study, the efficacy of a Cat K inhibitor in the reduction in tumour-induced osteolysis was found to be enhanced in the presence of the bisphosphonate zolendronic acid [35,36]. When prostate cancer cells were injected into the tibia of SCID mice, treatment with a Cat K inhibitor both prevented and diminished the progression of cancer growth in bone [37]. 

AP23451 administration to mice inoculated with MDA-231 breast cancer cells effectively prevents metastasis-induced osteolysis similar to bisphosphonate zoledronic (Zometa ). However, it also significantly reduces the volirme of tumor cells inside the bone marrow cavities of the mice as opposed to a lack of inhibitory effect on tirmor cell volume in mice treated with zoledronic acid. AP23588 is also a bone-targeted Src kinase inhibitor which has been determined to possess both anti-resorptive and anabohc properties in vitro with respect to reducing osteoclast activity and stimulating osteoblast activity, respectively. 

The three main alternatives to conventional UHMWPE represent the current state of the art in orthopedics, and are all expected to result in significant reductions in osteolysis. The ultimate goal for all of these alternative bearings is to reduce the incidence of revision for THA. Many years of clinical follow-up are still needed to verify the attainment of fhis long-term objective. 

Incidence and Significance of Osteolysis in Total Knee Arthroplasty... 

The incidence of osteolysis with cementless fixation has been reported as high as 30% within the first 5 years of implantation [47] (Table 8.3). In studies of cemented components, in contrast, the incidence of osteolysis is generally lower and has been reported to range between 0% and 20% (Table 8.3). In addition to the fixation method, implant factors (e.g., design [48-50]) and patient factors (e.g., obesity [51]) have been shown to have a significant influence on the incidence of osteolysis in TKA. 

Wear debris of conventional UHMWPE has been clearly associated with osteolysis and loosening of implants [46, 47]. Currently, clinical studies up to 5 years have corroborated the in vitro simulator testing results of significantly decreased wear in highly crosslinked UHMWPEs compared to conventional UHMWPE [41, 48, 49]. Currently, there is no conclusion on the differences in the biological activity of the wear debris from highly crosslinked... 

The clinical significance of in vivo oxidation continues to be a controversial topic for total hip replacement. In vivo oxidation, as a solitary factor, does not govern clinical failure modes of wear, osteolysis, and late implant loosening observed in historical, cemented total hip replacements (Chapter 5). The mechanical behavior of the UHMWPE liner in THA is but one variable in a complex multifactorial problem (Chapter 5). On the other hand, there is clear evidence of critical levels of oxidation in retrieved... 

Amstutz H, Campbell P, Kossovsky N, Qarke IC. Mechanism and clinical significance of wear debris-induced osteolysis. Clin Orthop RelatRes 1992 276 7-18. 

---