Bone metastases are common and severe complications of cancers. It is estimated to occur in 65–75% of breast and prostate cancer patients and cause 80% of breast cancer-related deaths. Metastasised cancer cells have devastating impacts on bone due to their ability to alter bone remodeling by interacting with osteoblasts and osteoclasts. Exercise, often used as an intervention for cancer patients, regulates bone remodeling via osteocytes. Therefore, we hypothesise that bone mechanical loading may regulate bone metastases via osteocytes. This provides novel insights into the impact of exercises on bone metastases. It will assist in designing cancer intervention programs that lowers the risk for bone metastases. Investigating the mechanisms for the observed effects may also identify potential drug targets.

MLO-Y4 osteocyte-like cells (gift of Dr. Bonewald, University of Missouri-Kansas City) on glass slides were placed in flow chambers and subjected to oscillatory fluid flow (1Pa; 1Hz; 2 hours). Media were extracted (conditioned media; CM) post-flow. RAW264.7 osteoclast precursors were conditioned in MLO-Y4 CM for 7 days. Migration of MDA-MB-231 breast cancer cells and PC3 prostate cancer cells towards CM was assayed using Transwell. Viability, apoptosis, and proliferation of the cancer cells in the CM were measured with Fixable Viability Dye eFluor 450, APOPercentage, and BrDu, respectively. P-values were calculated using Student's t-test.

Significantly more MDA-MB-231 and PC3 cells migrated towards the CM from MLO-Y4 cells with exposure to flow in comparison to CM from MLO-Y4 cells not exposed to flow. The preferential migration is abolished with anti-VEGF antibodies. MDA-MB-231 cells apoptosis rate was slightly lower in CM from MLO-Y4 cells exposed to flow, while proliferation rate was slightly higher. The current data showed no difference in cancer cells viability and adhesion to collagen between any two groups. On the other hand, it was observed that less MDA-MB-231 cells migrated towards CM from RAW264.7 cells conditioned in CM from MLO-Y4 cells stimulated with flow in comparison to those conditioned in CM from MLO-Y4 cells not stimulated with flow. TRAP staining results confirmed that there were less differentiated osteoclasts when RAW264.7 cells were cultured in CM from MLO-Y4 cells exposed to flow.

Overall, this study suggests that when only osteocytes and cancer cells are involved, osteocytes subjected to mechanical loading can promote metastases due to the increased secretion of VEGF. However, with the incorporation of osteoclasts, mechanical loading on osteocytes seems to reduce MDA-MB-231 cell migration. This is likely because osteocytes reduce osteoclastogenesis in response to mechanical stimulation, and osteoclasts have been shown to support cancer cells. Animal studies will also be conducted to verify the pro- or anti-metastatic effect of mechanical loading that is observed in the in vitro part of this study.

It is debatable whether high flexion total knee arthroplasty (TKA) designs will improve postoperative flexion, function or will diminish the need for manipulation under anesthesia (MUA). We retrospectively analyzed range of motion (ROM), flexion, Knee Society Score (KSS), and rate of MUA in a consecutive group of patients who underwent TKA with a conventional PS or a high flexion (HF) insert using identical surgical technique, implant design and postoperative care. Fifty TKAs with a standard posterior stabilized insert (PS) were matched with 50 who received a high flexion insert (HF) for patient’s age, gender, preoperative ROM, and KSS. The patient’s ROM and KSS were obtained at 6 weeks, 4 months, and 1 year postoperatively. The outcome variables (flexion, ROM, KSS and manipulation rate) in the two groups were compared using the generalized estimating equations method. A second analysis of patients with preoperative flexion equal or greater than 120 degrees was performed. The ROM, flexion, and patient reported KSS was similar in the PS and HF groups at each one of the time periods. The rate of MUA was also similar. Patients with a preoperative ROM of at least 120° showed similar results. Our study found that 1 year after surgery, patients who underwent TKA with a PS or a HF insert achieved similar flexion, ROM and function.

Introduction: Femoroacetabular impingement (FAI) is one of the main causes of hip osteoarthritis. Femoral retroversion has been reported as a cause of FAI and it is well established that a retroverted femur produces hip pain and alterations in the external and internal rotation balance. However, no studies of femoral retroversion in patients with FAI have been reported. Furthermore, since the lack of internal rotation is a common feature in patients with FAI, it could be possible that femoral version abnormalities are present in these patients. The purpose of this study is to describe the femoral version in a group of patients with FAI and to assess its relation in the development of hip osteoarthritis.

Methods: The history, x-rays and hip CT scans of 142 patients with FAI were reviewed. All patients presented persistent hip pain and were evaluated clinically between January 2006 and July 2008. We defined FAI when at least one of the following features were present:

an abnormal alpha angle (> 49°) measured on the elongated femoral neck x-ray,

We documented the type of FAI, the presence of acetabular dysplasia, coxa valga, coxa vara and the femoral version measured on the CT scan. The degree of osteoarthritis of the hip using the Tönnis classification was documented as well.

Results: Two hundred and sixty-five FAI hips from 142 patients (73 females and 69 males) were analyzed. The average age was 36.7 years. The mean femoral version was 11.4 ° (−14.1° to 47°). We found 43 hips (16.6%) of the femora were retroverted and 133 hips (50%) had either diminished anteversion (< 10°) or were retroverted. In 12 hips (0.05%) the only cause of FAI was the presence of a diminished anteversion or retroverted femur. The statistical analysis using the generalized estimating equations method including the right and left hips, shown that among these six predictors, both femoral retroversion (p=0.046) and coxa vara (p< 0.001) were statistically significant for the presence of osteoarthritis.

Conclusion: The presence of a retroverted femur seems to be a cofactor in the development of hip osteoarthritis in patients with FAI. The orthopedic surgeons should be aware of the high frequency of femoral retroversion when evaluating patients with hip impingement, in order to make the right diagnosis and treatment. It might be possible that this association between FAI and femoral retroversion is due to a common hip disease during skeletal maturation (i.e. SCFE) leading to two anatomical alterations at the proximal femur: reduced head-neck offset and retroverted femur.