Although aging has traditionally been viewed as the most important risk factor for osteoarthritis (OA), an increasing amount of epidemiological evidence has highlighted the association between metabolic abnormalities and OA, particularly in younger individuals. Metabolic abnormalities, such as obesity and type II diabetes, are strongly linked to OA, and they affect both weight-bearing and non-weight-bearing joints, thus suggesting that the pathogenesis of OA is more complicated than the mechanical stress induced by overweight. This review aims to explore the recent advances in research on the relationship between metabolic abnormalities and OA risk, including the impact of abnormal glucose and lipid metabolism, the potential pathogenesis and targeted therapeutic strategies.

Joint pain is the hallmark symptom of osteoarthritis (OA) and the main reason for patients to seek medical assistance. OA pain greatly contributes to functional limitations of joints and reduced quality of life. Although several pain-relieving medications are available for OA treatment, the current intervention strategy for OA pain cannot provide satisfactory pain relief, and the chronic use of the drugs for pain management is often associated with significant side effects and toxicities. These observations suggest that the mechanisms of OA-related pain remain undefined. The current review mainly focuses on the characteristics and mechanisms of OA pain. We evaluate pathways associated with OA pain, such as nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA), calcitonin gene-related peptide (CGRP), C–C motif chemokine ligands 2 (CCL2)/chemokine receptor 2 (CCR2) and tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, and the Wnt/β-catenin signaling pathway. In addition, animal models currently used for OA pain studies and emerging preclinical studies are discussed. Understanding the multifactorial components contributing to OA pain could provide novel insights into the development of more specific and effective drugs for OA pain management.

Polyetheretherketone (PEEK) is a desirable alternative to conventional biomedical metals for orthopedic implants due to the excellent mechanical properties. However, the inherent bioinertness of PEEK contributes to inferior osseointegration of PEEK implants, especially under pathological conditions of osteoporosis. Herein, a programmed surface is designed and fabricated on PEEK to dictate osteoimmunomodulation and bone regeneration sequentially. A degradable hybrid coating consisting of poly(lactide-co-glycolide) and alendronate (ALN) loaded nano-hydroxyapatite is deposited on PEEK and then interleukin-4 (IL-4) is grafted onto the outer surface of the hybrid coating with the aid of N₂ plasma immersion ion implantation and subsequent immersion in IL-4 solution. Dominant release of IL-4 together with ALN and Ca²⁺ during the first few days synergistically mitigates the early acute inflammatory reactions and creates an osteoimmunomodulatory microenvironment that facilitates bone regeneration. Afterwards, slow and sustained delivery of ALN and Ca²⁺ in the following weeks boosts osteogenesis and suppresses osteoclastogenesis simultaneously, consequently ameliorating bone-implant osseointegration even under osteoporotic conditions. By taking into account the different phases in bone repair, this strategy of constructing advanced bone implants with sequential functions provides customizable and clinically viable therapy to osteoporotic patients.