Causal relationship of serum nutritional factors with osteoarthritis: a Mendelian randomization study.

OBJECTIVES: OA is the most common form of arthritis worldwide and has a major impact on the quality of life among the older population. This study aimed at determining the potential causal effects of several serum nutritional factors on OA. METHODS: A total of seven serum nutritional factors were identified from genome-wide association studies. Summary statistics for OA were obtained from UK Biobank (194 153 for women and 166 988 for men) and a large genome-wide association studies meta-analysis based on the European population (455 221, 393 873 and 403 124 for overall, hip and knee OA, respectively). Two-sample Mendelian randomization approach was used to estimate the causal association between the selected nutritional factors and the risk of OA. RESULTS: The Mendelian randomization analyses suggested that serum calcium levels were inversely associated with overall OA (95% CI, 0.595, 0.850), hip OA (95% CI, 0.352, 0.799) and knee OA (95% CI, 0.461, 0.901). Serum retinol levels were also inversely associated with hip OA (95% CI, 0.257, 0.778). Moreover, sex-specific associations were observed between serum calcium levels (95% CI, 0.936, 0.998), iron levels (95% CI, 1.000, 1.012), selenium levels (95% CI, 0.923, 0.999) and OA in women. CONCLUSION: In this study, an inverse causal association between serum calcium levels and OA was established. Serum retinol levels were inversely associated with hip OA. In addition, we provide evidence for the causal effect of serum calcium, iron and selenium on the risk of OA in women.

Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity.

Excessive activation of osteoclast activity is responsible for many bone diseases, such as osteoporosis, rheumatoid arthritis, periprosthetic osteolysis, and periodontitis. Natural compounds that inhibit osteoclast formation and/or function have therapeutic potential for treating these diseases. Catalpol, a bioactive iridoid extracted from a traditional herbal medicine Rehmannia glutinosa, exhibits various pharmacological properties, including anti-inflammatory, antioxidant, antidiabetic, and antitumor effects. However, its effects on osteoclast formation and function remain unknown. In the present study, we showed that catalpol inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption, as well as the expression of osteoclast-related marker genes. The investigation of molecular mechanisms showed that catalpol upregulated phosphatase and tensin homolog (PTEN) activity by reducing its ubiquitination and degradation, subsequently suppressing RANKL-induced NF-κB and AKT signaling pathways, leading to an inhibition on NFATc1 induction. Furthermore, catalpol protected mice against inflammation- and ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo. These results suggest that catalpol might be developed as a promising candidate for treating osteoclast-related bone diseases.

Effects of sequential treatment with intermittent parathyroid hormone and zoledronic acid on particle-induced implant loosening: Evidence from a rat model.

Particle-induced implant loosening is a major challenge to long-term survival of joint prostheses. Administration of intermittent parathyroid hormone (PTH) has shown potential in the treatment of cases of early-stage periprosthetic osteolysis, while sequential administration of intermittent PTH (iPTH) and bisphosphonates (Bps) has achieved significant effects on treatment of postmenopausal osteoporosis. The objective of this study was to determine whether sequential treatment could preserve bone mass and implant fixation during a pathological course of peri-implant osteolysis in a rat model. Ninety male Sprague Dawley rats were randomly divided into nine groups, four of which were used for confirmation of establishment of the peri-implant osteolysis model at two time points, while the other five were used to determine the efficiency of the sequential treatment on peri-implant osteolysis. Implant fixation and peri-implant bone mass were evaluated using biomechanical testing, micro-CT analysis, and histology at 6 and 12 weeks postoperative. The biomechanical test demonstrated that the maximum loading force during a push-out test was significantly elevated in the sequential treatment group compared to the osteolysis group and iPTH withdrawal group at 12 weeks. Peri-implant bone morphology also indicated a robust increase in bone volume in the sequential treatment group. Sequential administration of iPTH and Bps was effective in preventing experimental peri-implant osteolysis, resulting in improved implant fixation and increased peri-implant bone volume. Clinical significance: The innovative application of sequential treatment in peri-implant osteolysis could be used clinically to improve the prognosis of patients with early-stage periprosthetic osteolysis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1489-1497, 2019.