Doxycycline for osteoarthritis of the knee or hip
ABSTRACT Osteoarthritis is a chronic joint disease that involves degeneration of articular cartilage. Pre-clinical data suggest that doxycycline might act as a disease-modifying agent for the treatment of osteoarthritis, with the potential to slow cartilage degeneration.
To examine the effects of doxycycline compared with placebo or no intervention on pain and function in patients with osteoarthritis of the hip or knee.
We searched CENTRAL ( The Cochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008, checked conference proceedings, reference lists, and contacted authors.
We included studies if they were randomised or quasi-randomised controlled trials that compared doxycycline at any dosage and any formulation with placebo or no intervention in patients with osteoarthritis of the knee or hip.
We extracted data in duplicate. We contacted investigators to obtain missing outcome information. We calculated differences in means at follow-up between experimental and control groups for continuous outcomes and risk ratios for binary outcomes.
We found one randomised controlled trial that compared doxycycline with placebo in 431 obese women. After 30 months of treatment, clinical outcomes were similar between the two treatment groups, with a mean difference of -0.20 cm (95% confidence interval (CI) -0.77 to 0.37 cm) on a visual analogue scale from 0 to 10 cm for pain and -1.10 units (95% CI -3.86 to 1.66) for function on the WOMAC disability subscale, which ranges from 17 to 85. These differences correspond to clinically irrelevant effect sizes of -0.08 and -0.09 standard deviation units for pain and function, respectively. The difference in changes in minimum joint space narrowing was in favour of doxycycline (-0.15 mm, 95% CI -0.28 to -0.02 mm), which corresponds to a small effect size of -0.23 standard deviation units. More patients withdrew from the doxycycline group compared with placebo due to adverse events (risk ratio 1.69, 95% CI 1.03 to 2.75).
The symptomatic benefit of doxycycline is minimal to non-existent. The small benefit in terms of joint space narrowing is of questionable clinical relevance and outweighed by safety problems. Doxycycline should not be recommended for the treatment of osteoarthritis of the knee or hip.
- SourceAvailable from: Sean E Gill
[Show abstract] [Hide abstract]
- "Furthermore, doxycyline at 2.0 mg/kg attenuates lung injury induced by LPS, doxycycline-resistant S. pneumoniae and bleomycin; and reduces inflammation in a model of asthma [4,5,14]. In humans, doxycycline has been used in the treatment of lymphangioleiomyomatosis (LAM) [15,16] and decreases proteinuria in diabetic nephropathy , although it was found to have no effect in osteoarthritis . Clearly, doxycycline has anti-inflammatory properties that are independent of its antimicrobial activity. "
ABSTRACT: Tetracyclines are broad-spectrum antibiotics that are also used to induce gene expression using the reverse tetracycline transactivator / tetracycline operator system (rtTA/tetO system). The system assumes that tetracyclines have no effects on mammals. However, a number of studies suggest that tetracyclines may have powerful anti-inflammatory effects. We report that the tetracycline, doxycycline, inhibits neutrophil (PMN) influx into the lungs of mice treated with bacterial endotoxin (LPS). Mice were challenged with intratracheal LPS in the presence or absence of doxycyline. bronchoalveolar lavage cell counts and differential, total bronchoalveolar lavage protein, lung homogenate caspase-3 and tissue imaging were used to assess lung injury. In addition, PMN chemotaxis was measured in vitro and syndecan-1 was measured in bronchoalveolar lavage fluid. The administration of doxycycline resulted in a significant decrease in the number of bronchoalveolar lavage PMNs in LPS-treated mice. Doxycycline had no effect on other markers of lung injury such as total bronchoalveolar lavage protein and whole lung caspase-3 activity. However, doxycycline resulted in a decrease in shed syndecan-1 in bronchoalveolar lavage fluid. We conclude that doxycycline has an important anti-inflammatory effect that can potentially confound the experiments in which the rtTA/tetO system is being used to study the immune response.Journal of Inflammation 09/2012; 9(1):31. DOI:10.1186/1476-9255-9-31 · 2.22 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Osteoarthritis (OA) is the most prevalent arthritis in the world with increasing numbers of people expected to acquire the disease as the population ages. Therapies commonly used to manage the disease have limited efficacy and some carry significant risks. Current data suggest that the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra) can alter the inflammatory response and cartilage erosion present in OA. Intra-articular gene expression of IL-1Ra has shown promising results in animal models to provide symptomatic improvement and minimize osteoarthritic changes. Orthogen AG (Dusseldorf, Germany) has developed a method to produce an autologous conditioned serum (ACS) rich in IL-1Ra marketed as Orthokine. Study participants treated with ACS have improved pain and function; however, these results are preliminary and need confirmation. If ongoing trials prove that ACS can retard cartilage degeneration and reduce inflammation, the management of OA would be dramatically altered, perhaps providing a mechanism to prevent the disease or at least its progression.Expert Review of Clinical Immunology 05/2010; 6(3):335-45. DOI:10.1586/eci.10.17 · 3.34 Impact Factor
Article: Emerging drugs for osteoarthritis[Show abstract] [Hide abstract]
ABSTRACT: INTRODUCTION: Osteoarthritis (OA), the most prevalent form of joint disease, affects as much as 13% of the world's population. In the USA, it is the leading cause of disability in people over age 65 and is characterized by progressive cartilage loss, bone remodeling, osteophyte formation and synovial inflammation with resultant joint pain and disability. There are no treatments marketed for structural disease modification; current treatments mainly target symptoms, with > 75% of patients reporting need for additional symptomatic treatment. AREAS COVERED: Drugs in later development (Phase II - III) for OA pain and joint structural degeneration are reviewed. Topics that are not covered in this article are procedural-based (e.g., arthrocentesis, physical therapy), behavioral-based (e.g., weight loss, pain coping techniques) or device-based (e.g., knee braces, surgical implants) treatments. EXPERT OPINION: More in-depth understanding of the pathophysiology of the disease, as well as elucidation of the link between clinical symptomatology and structural changes in the joint will likely lead to the development of novel target classes with promising efficacy in the future. Efficacy notwithstanding, there remain significant hurdles to overcome in clinical development of these therapeutics, inherent in the progression pattern of the disease as well as challenges with readouts for both pain and structure modification trials.Expert Opinion on Emerging Drugs 05/2011; 16(3):479-91. DOI:10.1517/14728214.2011.576670 · 3.28 Impact Factor