Osteoarthritis is a major source of pain, disability, and socioeconomic cost worldwide. Osteonecrosis is a disabling disorder that frequently occurs in the younger population aged from 20-50 years. The compound Eucommia bone tonic granules, a traditional Chinese medicine, can alleviate the damage of osteoarthritis and osteonecrosis.

To investigate the potential role of the compound Eucommia bone tonic granules (Eucommia) in the treatment of patients with osteoarthritis and osteonecrosis.

One-hundred forty osteoarthritis and osteonecrosis cases admitted to our hospital from January 2013 to December 2017 were selected. Patients were divided into two groups: Eucommia-meloxicam group and meloxicam group. Clinical efficacy and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score were evaluated according to the evaluation criteria of orthopedic diseases. The levels of bone-GLA protein, interleukin-17, recombinant human S100 calcium binding protein A12, sphingosine 1-phosphate, cystatin C, creatinine, and hemoglobin in peripheral blood were determined.

The total effective rate in the two osteoarthritis groups was not different, but the total effective rate in the two osteonecrosis groups was significantly different. The overall efficacy of Eucommia-meloxicam group was superior to that of the meloxicam group. WOMAC showed that pain, stiffness, and dysfunction in the two groups of osteoarthritis and osteonecrosis before and after treatment were significantly different. The concentration of recombinant human S100 calcium binding protein A12, sphingosine 1-phosphate, cystatin C, creatinine, and hemoglobin before and after treatment in the Eucommia-meloxicam group and meloxicam group of osteoarthritis and osteonecrosis were significantly different, and the two treatment groups were significantly different from each other for osteoarthritis.

Our findings indicate that Eucommia can effectively enhance the curative effect of meloxicam, and the combination of Eucommia and meloxicam is superior to meloxicam alone.

Osteoarthritis is a chronic degenerative disease of articular cartilage. Due to the special pathological location of bone joints, osteoarthritis can be diagnosed through imaging and relevant biochemical indicators[1-3]. The main pathological changes of osteoarthritis are cartilage matrix degradation, osteophyte hyperplasia, and osteophyte formation around cartilage[4]. Osteonecrosis is a disease caused by multiple factors that disrupt the blood supply of the femoral head, leading to the death of bone cells or the destruction of surrounding tissues, and finally causing joint surface collapse and osteoarthritis[5]. The traditional Chinese medicine Eucommia ulmoides Oliver (Eucommiaceae) can strengthen the spleen and tonify the kidney, stop stasis, and decrease turbidity.

Eucommia contains a variety of bioactive chemicals, including lignans, iridoids, phenolics, steroids, terpenoids, flavonoids, etc. These bioactive chemicals function effectively to nourish the liver and kidneys and regulate blood pressure and have been used to treat bone fractures and other bone diseases. The composition of bioactive chemicals extracted from Eucommia varies depending on the functional part (leaves, seeds, bark, and staminate flower) and planting models. The bioactive parts of Eucommia are widely used as raw materials for medicine and food, powdery extracts, herbal formulations, and tinctures. These capabilities hold potential for future development and commercial exploitation of the bioactive products from Eucommia[6].

The stem bark of Eucommiaceae, which is also known as Du-Zhong, is commonly utilized in traditional Chinese medicine for the treatment of rheumatoid arthritis[7]. Eucommia is the main component of the compound Du-Zhong bone tonic granules. Modern pharmacological and molecular biology studies have supported these traditional uses and suggest that crude extracts and total glycosides of Eucommia ulmoides may yield safe and mild anti-osteoporosis agents[8]. Eucommia may inhibit the progression of osteoarthritis by inhibiting the phosphoinositol 3-kinase/Akt pathway to delay cartilage degeneration, reduce inflammatory cytokines, and prevent matrix metalloproteinase-3 secretion[9]. Eucommia has a cartilage-protecting effect in rats with osteoarthritis, potentially by improving cartilage metabolism, regulating the degradation of the extracellular matrix of the articular cartilage, and inhibiting apoptosis in chondrocytes, thereby slowing down joint degeneration[10]. Limited data, however, has shown the effect of Eucommia on osteonecrosis.

Therefore, to investigate the potential role of Eucommia in the treatment of patients with osteoarthritis and osteonecrosis, we determined the effective rate, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and the levels of bone-GLA protein (BGP), interleukin-17 (IL-17), recombinant human S100 calcium binding protein A12 (S100A12), sphingosine 1-phosphate (SIP), cystatin C (Cysc), creatinine (SCr), and hemoglobin (Hb) in patients with osteoarthritis and osteonecrosis.

Osteoarthritis is a chronic disease in which the pathological processes start from the catabolism of cartilage extracellular matrix and next extend on the whole joint[11]. Osteonecrosis is an ischemic pathologic process associated with a number of conditions affecting a range of age groups[12]. Traditional Chinese medicine has been accepted as a complementary therapy for knee osteoarthritis, not only in Asian countries[11,13], but also in the West, which might result from its effects on pain, loss of mobility and function, as well as depression.

In this study, the results showed that the total effective rate in the two groups of osteoarthritis was not significantly different, but that the total effective rate in the two groups of osteonecrosis was significantly different. The overall efficacy in the Eucommia-meloxicam group was superior to that in the meloxicam group, indicating that Eucommia can effectively enhance the curative effect of meloxicam.

The WOMAC score data revealed that pain, stiff, and dysfunction in the two groups of osteoarthritis and osteonecrosis before and after treatment were significantly different, indicating that Eucommia and meloxicam can effectively alleviate pain, stiff, and dysfunction in patients with osteoarthritis and osteonecrosis. When comparing WOMAC score of pain between the osteoarthritis and osteonecrosis groups, treatment was significant, indicating that the effect in the Eucommia-meloxicam group was superior to that of the meloxicam group. The combination of Eucommia and meloxicam had a better effect on the osteoarthritis and osteonecrosis than meloxicam alone. Another study by Hussain et al[14] found that meloxicam combined with resveratrol could also alleviate the disease of patients, because it could improve hepatic and renal function and relieve pain, which is consistent with our research results.

The concentration of the S100A12, SIP, Cysc, SCr, and Hb in the Eucommia-meloxicam group and meloxicam group of osteoarthritis and osteonecrosis were significantly different before and after treatment and in the two group of osteoarthritis, the treatments were significant. This finding indicates that Eucommia can enhance the effect of meloxicam in patients with osteoarthritis and osteonecrosis and that combining Eucommia and meloxicam is better than meloxicam alone.

However, this study still has certain limitations. Firstly, as a retrospective study, a long-term and multi-time point follow-up to the patients was not conducted. Secondly, the mechanism of Eucommia ulmoides on osteoarthritis remains unclear. Therefore, we hope to conduct more experiments and include follow-up in future studies to observe further the mechanism of Eucommia ulmoides in osteoarthritis, thus supplementing our research results.

Our data indicate that Eucommia can effectively enhance the curative effect of meloxicam, and the combination of the Eucommia and meloxicam is better than meloxicam alone. It is an effective drug for the treatment of osteoarthritis and osteonecrosis.