The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs.

Phosphocitrate (PC) and its analogue, PC-β ethyl ester, inhibit articular cartilage degeneration in Hartley guinea pigs. However, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the hypothesis that PC exerted its disease-modifying effect on osteoarthritis (OA), in part, by inhibiting a molecular program similar to that in the endochondral pathway of ossification.

Eight Hundred Twenty-Five Medial Mobile-Bearing Unicompartmental Knee Arthroplasties: The First 10-Year US Multi-Center Survival Analysis.

Background: FDA approval for the Oxford phase III device was approved for use in the United States in 2004. This study seeks to provide the first long-term, large patient sample size, Oxford phase III multi-site survivorship study in the United States, investigating patient reported outcomes of pain and function, while also providing an in-depth analysis of causes for revision, and finally addressing recent advancements that can help aid the unicompartmental knee arthroplasty (UKA) process and further improve partial knee survivorship.

Methods: Between July 2004 and December 2006, 5 surgeons from around the United States performed medial UKA through the minimally invasive surgical approach, on 825 knees in 695 patients.

Biological Effects of Phosphocitrate on Osteoarthritic Articular Chondrocytes.

Background: Phosphocitrate (PC) inhibits osteoarthritis (OA) in Hartley guinea pigs. However, the underlying molecular mechanisms remain poorly understood.

Objective: This study sought to examine the biological effect of PC on OA chondrocytes and test the hypothesis that PC may exert its OA disease modifying effect, in part, by inhibiting the expression of genes implicated in OA disease process and stimulating the production of extracellular matrices.

Biological effects and osteoarthritic disease-modifying activity of small molecule CM-01.

Phosphocitrate inhibits cartilage degeneration, however, the prospect of phosphocitrate as an oral disease modifying drug might be limited. The purpose of this study was to investigate the biological effects and disease-modifying activity of a phosphocitrate "analog," CM-01 (Carolinas Molecule-01), and test the hypothesis that CM-01 is a disease modifying drug for osteoarthritis therapy. The effects of CM-01 on calcium crystal-induced expression of matrix metalloproteinase-1 and interleukin-1 beta, cell-mediated calcification and production of proteoglycan by chondrocytes were examined in cell cultures.

Patient-Directed Valgus Stress Radiograph of the Knee: A New and Novel Technique.

The radiographic investigation of patients with medial-compartment osteoarthritis of the knee is a critical element in the decision-making process of determining whether the patient is a candidate for unicompartmental or total knee arthroplasty. A valgus stress radiograph of the affected knee is an essential part of this radiographic investigation. Historically, this has been performed with manual stress applied by the surgeon or the radiologic technologist; thus, this examination requires 2 individuals to complete.

Disease-modifying effects of phosphocitrate and phosphocitrate-β-ethyl ester on partial meniscectomy-induced osteoarthritis.

Background: It is believed that phosphocitrate (PC) exerts its disease-modifying effects on osteoarthritis (OA) by inhibiting the formation of crystals. However, recent findings suggest that PC exerts its disease-modifying effect, at least in part, through a crystal-independent action. This study sought to examine the disease-modifying effects of PC and its analogue PC-β-ethyl ester (PC-E) on partial meniscectomy-induced OA and the structure-activity relationship.

Cartilage Degeneration, Subchondral Mineral and Meniscal Mineral Densities in Hartley and Strain 13 Guinea Pigs.

Osteoarthritis is a joint disease involved in articular cartilage, subchondral bone, meniscus and synovial membrane. This study sought to examine cartilage degeneration, subchondral bone mineral density (BMD) and meniscal mineral density (MD) in male Hartley, female Hartley and female strain 13 guinea pigs to determine the association of cartilage degeneration with subchondral BMD and meniscal MD. Cartilage degeneration, subchondral BMD and meniscal MD in 12 months old guinea pigs were examined with histochemistry, X-ray densitometry and calcium analysis.

Early Fracture of a Vitamin-E-Infused, Highly Cross-Linked Polyethylene Liner After Total Hip Arthroplasty: A Case Report.

Case: A vitamin-E-infused, highly cross-linked ultra-high molecular weight polyethylene (HXLPE) acetabular liner fractured without trauma less than twelve months after its implantation in a seventy-one-year-old woman.

Conclusion: The remelting process utilized in the production of many commercially available HXLPE acetabular liners causes an immediate reduction in the fracture toughness of the material; however, it provides the benefit of oxidative stability, which prevents the loss of beneficial mechanical properties over time. Vitamin-E-infused HXLPE avoids the immediate decrease in fracture toughness by avoiding the remelting process.

Expression of phosphocitrate-targeted genes in osteoarthritis menisci.

Phosphocitrate (PC) inhibited calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms remain elusive. This study sought to determine PC targeted genes and the expression of select PC targeted genes in OA menisci to test hypothesis that PC exerts its disease modifying activity in part by reversing abnormal expressions of genes involved in OA.

Fibroblast-like synoviocytes induce calcium mineral formation and deposition.

Calcium crystals are present in the synovial fluid of 65%-100% patients with osteoarthritis (OA) and 20%-39% patients with rheumatoid arthritis (RA). This study sought to investigate the role of fibroblast-like synoviocytes (FLSs) in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla) protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs.

Biological activities of phosphocitrate: a potential meniscal protective agent.

Phosphocitrate (PC) inhibited meniscal calcification and the development of calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the mechanisms remain elusive. This study sought to examine the biological activities of PC in the absence of calcium crystals and test the hypothesis that PC is potentially a meniscal protective agent.

Phosphocitrate is potentially a disease-modifying drug for noncrystal-associated osteoarthritis.

Phosphocitrate (PC), a calcification inhibitor, inhibits the development of crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms underlying its disease-modifying effect remain elusive. This study sought to test the hypothesis that PC has calcium crystal-independent biological activities which are, at least in part, responsible for its disease-modifying activity.

Histological examination of collagen and proteoglycan changes in osteoarthritic menisci.

This study sought to examine collagen and proteoglycan changes in the menisci of patients with osteoarthritis (OA). Collagens were examined using picrosirius red, and hematoxylin and eosin. Proteoglycans were examined using safranin-O and alcian blue.

Meniscal calcification, pathogenesis and implications.

Purpose Of Review: The purpose of this review is to discuss recent advances in the understanding of the nature of meniscal calcification and its relationships with meniscal degeneration and cartilage lesions in osteoarthritis.

Recent Findings: Calcium crystals are universally present in hyaline articular cartilage, as well as the meniscus of the knee of end-stage osteoarthritis patients. Osteoarthritis meniscal cells display a distinct gene-expression profile different from normal meniscal cells, have elevated expression of ankylosis progressive analog (ANKH) and ectonucleotide pyrophosphatase/phosphodiesterase1 (ENPP1) and produce more calcium minerals than normal meniscal cells in vitro.

Calcium deposition in osteoarthritic meniscus and meniscal cell culture.

Introduction: Calcium crystals exist in the knee joint fluid of up to 65% of osteoarthritis (OA) patients and the presence of these calcium crystals correlates with the radiographic evidence of hyaline cartilaginous degeneration. This study sought to examine calcium deposition in OA meniscus and to investigate OA meniscal cell-mediated calcium deposition. The hypothesis was that OA meniscal cells may play a role in pathological meniscal calcification.

Analysis of meniscal degeneration and meniscal gene expression.

Background: Menisci play a vital role in load transmission, shock absorption and joint stability. There is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, and 2) to examine gene expression in OA meniscal cells compared to normal meniscal cells.

Telomerase transduced osteoarthritis fibroblast-like synoviocytes display a distinct gene expression profile.

Objective: To examine the differential gene expression in telomerase transduced osteoarthritis fibroblast-like synoviocytes (hTERT-OA 13A FLS) and telomerase transduced rheumatoid arthritis FLS (hTERT-RA 516 FLS) and test the hypothesis that longterm culture of hTERT-OA 13A FLS display a disease-specific gene expression profile.

Methods: Gene expression in passage 8 hTERT-OA 13A FLS and passage 8 hTERT-RA 516 FLS were compared using microarray assays. Differential expression of selected genes was further examined by reverse transcription-polymerase chain reaction (RT-PCR).

Cementation of polyethylene liners into well-fixed metal shells at the time of revision total hip arthroplasty.

Cementing polyethylene liners into well-fixed metal shells at revision total hip arthroplasty is an accepted technique. Previous studies have tested the initial strength of this construct, but none have tested the construct under physiologic and abnormal loading conditions. The current study examines liner-shell performance under these conditions.

Tibial post failures in a condylar posterior cruciate substituting total knee arthroplasty.

In posterior-stabilized total knee arthroplasties, a femoral cam and polyethylene tibial post are commonly used to restore posterior stability after sacrifice of the posterior cruciate ligament. This article reports a high incidence of early tibial post failures in one design of prosthesis and examines the variables that may have contributed to such. Five hundred sixty-four consecutive posterior-stabilized total knees were implanted in 512 patients, using a total knee prosthesis with a polyethylene tibial post and femoral cam.

Patient out-of-pocket expenses in major orthopedic procedures: total hip arthroplasty as a case study.

Total hip arthroplasty (THA) is a successful procedure for improving quality of life. There are few publications regarding out-of-pocket expenses incurred by individuals undergoing uncomplicated THA. Detailed billing and record reviews and patient phone surveys were conducted on 34 Medicare patients identifying charges and reimbursements recorded by the health care system and all out-of-pocket expenses incurred by patients undergoing uncomplicated THA (diagnostic related group [DRG] 209/current procedural terminology [CPT] 27130).

Impact of anaesthesia-surgery on D-dimer concentration and end-tidal CO2 and O2 in patients undergoing surgery associated with high risk for pulmonary embolism.

Background: The exhaled end-tidal CO2/O2 ratio and the D-dimer concentration are diagnostic markers of pulmonary embolism (PE).

Objective: To develop a non-invasive technique to monitor for PE in surgical patients. We examine the change imparted by anaesthesia-surgery on the end-tidal CO2/O2 compared with the D-dimer.

Pay-for-performance in orthopedics: implications for clinical practice.

The United States health care system currently faces many challenges, including rising costs and variable quality. Health care purchasers and payers are demanding increased transparency and accountability for their health care dollars. Pay-for-performance (P4P) initiatives, which seek to link provider reimbursement to measures of quality and efficiency, have been introduced by both private and government payers.

Outcomes research in total joint replacement: a critical review and commentary.

The ostensible goal of outcomes research is to demonstrate the effectiveness of total joint replacement as it relates to appropriate use of health care resources and quality of care. Modern outcomes assessment focuses on identifying reproducible and valid instruments that can be used to collect and analyze patient outcomes. Validation of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) has had a major impact on obtaining meaningful outcomes data.

Cementless titanium tapered-wedge femoral stem: 10- to 15-year follow-up.

This investigation is an ongoing clinical and radiographic analysis of a titanium tapered-wedge femoral component with a proximal plasma-spray porous coating. Integral femoral stems (Biomet, Warsaw, IN) were implanted in 200 hips in 186 patients. Nineteen patients died before 10-year follow-up, and 50 patients were lost to follow-up.