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

Heide, Huub J. L. van der; Rijnberg, W. J.; Sorge, Adriaan van; Kampen, A. van; Schreurs, B.W.

doi:10.1080/17453670610013475

Cited by 37 publications

(33 citation statements)

References 31 publications

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“…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: 72%

Regulation of chondrogenesis and chondrocyte differentiation by stress

Zuscik¹,

Hilton²,

Zhang³

et al. 2008

J. Clin. Invest.

216

173

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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...

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Section: The Influence Of Pathologic Stress On Chondrogenesis and Endsupporting

confidence: 72%

Regulation of chondrogenesis and chondrocyte differentiation by stress

Zuscik¹,

Hilton²,

Zhang³

et al. 2008

J. Clin. Invest.

216

173

View full text Add to dashboard Cite

show abstract

“…By exposing only a small group of patients, they studied the efficacy of rofecoxib (a COX-2 in inhibitor) to prevent HO. These positive results were confirmed later in a randomised controlled trial using a large patient cohort [14]. For calculation of the number of subjects needed in this two-stage study design, the data of two historical patient groups with total hip arthroplasty from our department were used [15].…”

Section: Two-stage Study Designmentioning

confidence: 83%

“…In a previous study that was performed by our research group, we found Rofecoxib, a selective COX-2 inhibitor, equally effective as indomethacin to prevent HO after THA [13,14]. However, serious concerns were raised over the safety of this selective COX-2 inhibitor for the cardiovascular system.…”

Section: Discussionmentioning

confidence: 99%

Is etoricoxib effective in preventing heterotopic ossification after primary total hip arthroplasty?

Brunnekreef

Hoogervorst

Ploegmakers

et al. 2013

International Orthopaedics (SICOT)

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Purpose Heterotopic ossification is a common complication after total hip arthroplasty. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to prevent heterotopic ossifications effectively, however gastrointestinal complaints are reported frequently. In this study, we investigated whether etoricoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor that produces fewer gastrointestinal side effects, is an effective alternative for the prevention of heterotopic ossification. Methods We investigated the effectiveness of oral etoricoxib 90 mg for seven days in a prospective two-stage study design for phase-2 clinical trials in a small sample of patients (n=42). A cemented primary total hip arthroplasty was implanted for osteoarthritis. Six months after surgery, heterotopic ossification was determined on anteroposterior pelvic radiographs using the Brooker classification. Results No heterotopic ossification was found in 62 % of the patients that took etoricoxib; 31 % of the patients had Brooker grade 1 and 7 % Brooker grade 2 ossification. Conclusions Etoricoxib seems effective in preventing heterotopic ossification after total hip arthroplasty. This finding further supports the use of COX-2 inhibitors for the prevention of heterotopic ossification following total hip arthroplasty.

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“…The results showed a 59% reduction (95% CI: 54%, 64%) in the risk of heterotopic ossification after hip arthroplasty in NSAID-treated patients. Recent clinical trials have reported that COX-2-selective NSAIDs are also effective in preventing heterotopic ossification after hip joint replacement [51][52][53][54].…”

Section: Heterotopic Ossificationmentioning

confidence: 99%

Non‐Steroidal Anti‐Inflammatory Drugs, Cyclooxygenase‐2 and the Bone Healing Process

Vuolteenaho

Moilanen

2007

Basic Clin Pharma Tox

169

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Traditional non-steroidal anti-inflammatory drugs (NSAID) and selective cyclooxygenase-2 (COX-2) inhibitors are widely used in the treatment of pain, including bone fracture pain and orthopaedic post-operative pain. The gastrointestinal and cardiovascular adverse effects of NSAIDs are acknowledged, but their effects on bone are less widely known.Prostaglandins play an important role in the regulation of osteoblast and osteoclast functions, and inhibition of prostaglandin production retards bone formation. Therefore, NSAIDs could be expected to have significant consequences in divergent clinical situations where bone formation or remodelling is a contributing factor. The present survey reviews current experimental and clinical evidence related to two of those conditions (i.e. on ectopic bone formation and on bone fracture healing). NSAIDs are used clinically to prevent ectopic bone formation (also known as heterotopic ossification) (e.g. after total hip arthroplasty or trauma). The efficacy of NSAIDs in the avoidance of heterotopic ossification has been documented in controlled clinical trials, but the inherent risks (e.g. on healing processes and on loosening of prostheses) need further studies. At the same time, NSAIDs are widely used in the treatment of fracture pain, and their inhibitory effects on the ongoing bone healing process have raised concerns. Results of fracture healing studies in animals treated with NSAIDs or in mice lacking COX-2 gene show that inhibition or deficiency of COX-2 impairs the bone healing process. The limited clinical data also support the assumption that inhibition of COX-2 by non-selective or COX-2-selective NSAIDs delays fracture healing. However, the clinical significance of the effect in various patient groups needs to be carefully assessed and further investigations are needed to characterize the patients at the highest risk for NSAID-induced delayed fracture healing and its complications. In the meantime, use of NSAIDs in fracture patients should be cautious, keeping in mind the benefits of pain relief and inhibition of ectopic bone formation on one hand, and the risks of non-union and retarded union on the other hand.

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

Cited by 37 publications

References 31 publications

Regulation of chondrogenesis and chondrocyte differentiation by stress

Regulation of chondrogenesis and chondrocyte differentiation by stress

Is etoricoxib effective in preventing heterotopic ossification after primary total hip arthroplasty?

Non‐Steroidal Anti‐Inflammatory Drugs, Cyclooxygenase‐2 and the Bone Healing Process

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