Selective COX-2 inhibitor versus indomethacin for the prevention of heterotopic ossification after hip replacement: A double-blind randomized trial of 100 patients with 1-year follow-up

Grohs, Josef G.; Schmidt, Maximilian; Wanivenhaus, A.

doi:10.1080/17453670610013484

Cited by 48 publications

(43 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, COX-2 induction of PGE 2 production and signaling through PKA in muscle stem cells is a possible link between the inflammatory response to injury and ectopic bone formation. Although these studies have not involved the use of muscle stem cells, recent human data demonstrating that inhibition of COX-2 prevents heterotopic bone formation following hip arthroplasty are consistent with these findings (78)(79)(80).…”

Section: The Influence Of Pathologic Stress On Chondrogenesis and Endsupporting

confidence: 54%

Regulation of chondrogenesis and chondrocyte differentiation by stress

Zuscik¹,

Hilton²,

Zhang³

et al. 2008

J. Clin. Invest.

209

173

View full text Add to dashboard Cite

Chondrogenesis and endochondral ossification are the cartilage differentiation processes that lead to skeletal formation and growth in the developing vertebrate as well as skeletal repair in the adult. The exquisite regulation of these processes, both in normal development and in pathologic situations, is impacted by a number of different types of stress. These include normal stressors such as mechanical loading and hypoxia as well pathologic stressors such as injury and/or inflammation and environmental toxins. This article provides an overview of the processes of chondrogenesis and endochondral ossification and their control at the molecular level. A summary of the influence of the most well-understood normal and pathologic stressors on the differentiation program is also presented. Introduction to cartilageCartilage is a connective tissue that is comprised primarily of matrix (mainly collagens and proteoglycans) containing relatively sparse populations of chondrocytes, which perform matrix-generation and maintenance functions. During the development and growth of vertebrates, chondrogenesis is the dynamic cellular process that leads to the establishment of various types of cartilage, including hyaline, fibrous, and elastic cartilage. Hyaline cartilage is found in craniofacial structures, the trachea and bronchial tubes, the articular surfaces of diarthrodial joints, and the growth plate (GP) of long bones. GPs are responsible for driving the process of limb lengthening and bone growth during development pre- and postnatally. This type of bone growth involves the process of endochondral ossification (otherwise known as bone formation). The type of cartilage that is most prominent and most susceptible to both normal and pathologic forms of stress is the hyaline cartilage of the limb and trunk skeleton, which originates from the differentiation of condensed mesenchymal cells into clusters of cartilage cells known as chondrocytes. These cartilage anlagen preform the skeleton and provide a framework for endochondral bone development, a process that involves chondrocyte maturation and matrix mineralization in the GPs. The cells of each skeletal element proceed through a multi-step differentiation process generating both the mature GP cartilage, which controls skeletal growth during early and adolescent development, and the permanent articular cartilage (AC) found at the joint surface of all long bones.The processes of chondrogenesis and endochondral bone formation are not restricted to the developing skeletal system. In fact, following stress-related injuries, such as fractures of endochondral bone, the developmental programs of chondrogenesis and chondrocyte proliferation, maturation, hypertrophy, and terminal differentiation are reinitiated at the site of injury. Additionally, stress-related cartilage diseases such as osteoarthritis (OA) also have marked effects on the differentiation and maintenance of AC during adult life. This is why much attention has been paid to studying the cellular and molecular mechanism...

show abstract

Section: The Influence Of Pathologic Stress On Chondrogenesis and Endsupporting

confidence: 54%

Regulation of chondrogenesis and chondrocyte differentiation by stress

Zuscik¹,

Hilton²,

Zhang³

et al. 2008

J. Clin. Invest.

209

173

View full text Add to dashboard Cite

show abstract

“…A similar study, which we were unaware of, is also published in this issue of Acta Orthopaedica (Grohs et al 2007). The other study shows the same results as ours, but the incidence of HO was much higher in both treatment arms.…”

Section: Note Added In Proofmentioning

confidence: 96%

Similar effects of rofecoxib and indomethacin on the incidence of heterotopic ossification after hip arthroplasty

et al. 2007

View full text Add to dashboard Cite

Background Although indomethacin is effective in preventing heterotopic ossification (HO) after primary total hip arthroplasty, side effects are frequently observed. In the last decade a new class of drugs-the COX-2 selective nonsteroidal anti-inflammatory drugs-has been developed. To investigate the effect of these COX-2 selective NSAIDs on heterotopic ossification (HO) after primary total hip arthroplasty (THA), we conducted a randomized controlled trial using either indomethacin or rofecoxib for 7 days.Methods 186 patients received either indomethacin 3 times daily, or rofecoxib twice, and 1 placebo, daily for 7 days. HO was graded according to the 1-year postoperative radiographs according to the Brooker classification.Results 12 of the 186 patients included discontinued their medication before the end of the trial due to side effects. The remaining 174 patients were included in the analysis. In the indomethacin group (n = 89), 77 patients (87%) showed no HO, 9 showed HO of grade 1 and 3 showed HO of grade 2 according to the Brooker classification. In the rofecoxib group (n = 85) 73 patients (86%) showed no ossification, 9 showed grade 1, and 3 showed grade 2.Interpretation The prophylactic effect of rofecoxib for 7 days in preventing heteropic ossification after primary total hip arthroplasty is comparable to the effect of indomethacin given for 7 days. These results indicate that the development of HO follows a COX-2 pathway.

show abstract

“…In orthopaedic surgery the use of NSAIDs is under debate, as systemic NSAID treatment delays spinal fusion in patients and animal models (Thaller et al, 2005) and fracture healing of the long bones (Goodman et al, 2002;Gerstenfeld et al, 2003;Simon and O'Connor, 2007;Herbenick et al, 2008). This property of NSAIDs is, however, exploited in the clinic to prevent periprosthetic heterotopic calcifi cation after hip surgery (Grohs et al, 2007). The action of NSAIDs has been studied in the context of osteogenesis, and several observations link prostaglandin E 2 (PGE 2 ) and COX-2 to osteoblast differentiation (Zhang et al, 2002;Einhorn, 2003;Arikawa et al, 2004;Xie et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification

Welting

Caron²,

Emans

et al. 2011

eCM

View full text Add to dashboard Cite

Skeletogenesis and bone fracture healing involve endochondral ossification, a process during which cartilaginous primordia are gradually replaced by bone tissue. In line with a role for cyclooxygenase-2 (COX-2) in the endochondral ossifi cation process, non-steroidal anti-inflammatory drugs (NSAIDs) were reported to negatively affect bone fracture healing due to impaired osteogenesis. However, a role for COX-2 activity in the chondrogenic phase of endochondral ossifi cation has not been addressed before. We show that COX-2 activity fulfi ls an important regulatory function in chondrocyte hypertrophic differentiation. Our data reveal essential cross-talk between COX-2 and bone morphogenic protein-2 (BMP-2) during chondrocyte hypertrophic differentiation. BMP-2 mediated chondrocyte hypertrophy is associated with increased COX-2 expression and pharmacological inhibition of COX-2 activity by NSAIDs (e.g., Celecoxib) decreases hypertrophic differentiation in various chondrogenic models in vitro and in vivo, while leaving early chondrogenic development unaltered. Our fi ndings demonstrate that COX-2 activity is a novel factor partaking in chondrocyte hypertrophy in the context of endochondral ossifi cation and these observations provide a novel etiological perspective on the adverse effects of NSAIDs on bone fracture healing and have important implications for the use of NSAIDs during endochondral skeletal development.

show abstract

Selective COX-2 inhibitor versus indomethacin for the prevention of heterotopic ossification after hip replacement: A double-blind randomized trial of 100 patients with 1-year follow-up

Cited by 48 publications

References 12 publications

Regulation of chondrogenesis and chondrocyte differentiation by stress

Regulation of chondrogenesis and chondrocyte differentiation by stress

Similar effects of rofecoxib and indomethacin on the incidence of heterotopic ossification after hip arthroplasty

Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification

Contact Info

Product

Resources

About