Significance of Increased Leptin Expression in Osteoarthritis Patients
April
Significance of Increased Leptin Expression in Osteoarthritis Patients
Ping Zhang 0 1 2 3 4
Zhi-Hong Zhong 0 1 2 3 4
Hao-Tao Yu 0 1 2 3 4
Bin Liu 0 1 2 3 4
0 Accepted: March 1 , 2015
1 Received: June 8 , 2014
2 Academic Editor: Erica Villa, University of Modena & Reggio Emilia , ITALY
3 1 Department of Orthopedics, The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou, 510000 , P.R. China , 2 Department of Orthopedics, The Third Affiliated Hospital, Sun Yat-Sen University , Guangzhou, 510000 , P.R. China
4 Expression of Leptin and OA
Alterations in leptin expression contributes to the progression of various diseases, including cancers. This meta-analysis investigated the clinical significance of leptin levels in osteoarthritis (OA) patients, with the goal of building a leptin-based diagnostic criterion for OA.
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Competing Interests: The authors have declared
that no competing interests exist.
Multiple scientific databases in English and Chinese languages, such as the Cochrane
Library Database, CINAHL, Chinese Biomedical (CBM), EMBASE, PubMed, and Web of
Science, were exhaustively searched, without any language restrictions, to identify high-quality
studies relevant to leptin and OA. Version 12.0 STATA software was used for data analysis.
We used odds ratios (OR) and 95% confidence intervals (CI) to test the correlation between
serum leptin levels and OA progression.
A total of 11 clinical studies were finally selected for their high quality and relevance to the
topic in this meta-analysis. The 11 case-control studies contained a combined total of 3,625
subjects. The meta-analysis results showed that leptin expression was significantly increased
in OA patients, compared with the controls (SMD = 0.87, 95%CI: 0.72-1.02, P < 0.001), and
there was also a strong association between leptin expression levels and gender (SMD =
8.55, 95%CI: 4.74-12.35, P < 0.001). In ethnicity-stratified subgroup analysis, all the study
populations, irrespective of ethnicity, showed remarkably high leptin expression levels in
females and in OA patients (all P < 0.05), compared to their respective counterparts.
The present study revealed that increased leptin expression levels are associated with
disease severity in OA patients, especially among the female OA patients. Based on our
results, we propose that leptin level may be a useful biomarker for the assessment of the
clinical status in OA patients.
Osteoarthritis (OA) is the most prevalent type of arthritis and is a painful degenerative joint
disease involving cartilage and surrounding tissues, with a high incidence among elderly
populations, especially among older females [1]. OA prevalence is approximately 40% in adults aged
70 and over, and is the major cause of pain as well as disability in this age group, particularly in
women [2]. OA is mainly caused by an imbalance in the equilibrium between breakdown and
repair of joint tissues, resulting in aberrant repair or insufficient self-repair of injured synovial
joint tissues [3]. OA is characterized by consistent focal damage in the articular cartilage, as
well as mild synovitis, muscle weakness, meniscal tears, and appositional new bone formation
[4]. In addition, remodeling of osteophytes, sclerosis of the growth plate and subchondral
trabeculae are also typically observed in OA. Due to the multi-factorial nature of the underlying
OA pathogenesis, the etiology of OA is suspected to involve a complex interaction between the
environmental factors and intrinsic risk factors [5]. The environmental factors include obesity,
gender, mechanical stress, age, and joint trauma, with all of these playing pivotal roles in OA
origin, but obesity appears to be a common and an essential component in OA pathogenesis
[57]. Several previous studies have addressed the correlation between OA and
pro-inflammatory mediators, and proposed a role for leptin, which is closely correlated with obesity, as a
biomarker in OA [4,8].
Leptin is a ubiquitous 16-kDa pleiotropic protein primarily secreted by placenta or white
adipose tissue [9]. Leptin controls adipose tissue volumes and body mass index (BMI) through
regulating food intake and stimulating energy expenditure at the hypothalamus level, as a
negative feedback loop at the hypothalamic nuclei [6,10]. Leptin is implicated in regulation of
female endocrine reproductive system, and other biological pathways linked to immune
responses, inflammatory diseases, cardiovascular functions and in respiratory pathophysiology.
With specific relevance to bone diseases, leptin plays an indispensible role as a regulator of
bone growth via the induction of collagen synthesis, mineralization of bone, proliferation of
osteoblast, as well as the stimulation of endochondral ossification [11]. However, in clinical
practice, high level of leptin expression is found in many diseases, including Alzheimer disease,
breast cancer, and coronary heart diseases [12,13]. Recent studies also reported t (...truncated)