Table 1.

Pharmacotherapeutic options for osteoarthritis treatment.

Classification	Name	Indications	Pharmacological mechanisms	Side effects	References
Traditional medications	Acetaminophen	Relief mild to moderate pain relief	Inhibit COX-3 activity and synthesizing prostaglandin.	Liver damage; liver toxicity; transient liver enzyme elevations and hepatotoxicity	(3, 4, 11–15)
	Non-steroidal anti-inflammatory drugs (NSAIDs)	Relief mild to moderate pain; analgesic and anti-inflammatory	Inhibit cyclooxygenase enzymes and prostaglandin synthesis; inhibit COX-1 and COX-2 activity	Gastrointestinal complications, Kidney disease and adverse cardiovascular events	(13, 16–22)
	Opioid analgesics	Pain relief	Inhibit pain pathways in the central nervous system	Nausea, vomiting, headache, constipation, fatigue and drowsiness	(3, 18, 23–27)
	Serotonin-norepinephrine reuptake inhibitors (SNRIs)	Treatment of depression and mood disorder	Inhibit serotonin-norepinephrine reuptake	Fatigue and somnolence; sexual dysfunction; gastrointestinal problems	(28–32)
	Intra-articular injections of corticosteroids	Relief moderate-to-severe pain and inflammation	Down-regulate genetic expression of pro-inflammatory proteins; decrease inflammatory markers and cytokines	Post-injection pain and flushing; septic arthritis; possible rare Tachon syndrome	(33–38)
	Vitamin D supplements	Reduction of WOMAC pain and WOMAC function; reduction of VAS pain	Increase calcium absorption and have effects on cartilage and bone metabolism	No severe safety issues were reported	(39–42)
	Glucosamine and chondroitin sulfate supplements	Management of the symptoms of OA	Inhibit catabolic enzymes activities, and reduce IL-1 β levels in synovial fluids	No severe safety issues were reported	(15, 43–48)
	Antioxidant supplements	Pain relief and function improvement in knee OA	Inhibit reactive oxygen species signal transduction	Large-scale RCTs are needed	(49–52)
Emerging medications	Bone morphogenetic protein-7 (BMP-7)	Limit progression of osteoarthritis; treat bone nonunion and spinal fusion	Promote embryogenesis, improve bone and cartilage formation and repair	No adverse effects were found	(53–56)
	Fibroblast growth factor-18 (FGF-18)	Target cartilage for knee OA	Promote chondrogenesis and cartilage repair; increase cartilage thickness	No severe safety issues were reported	(57–59)
	Human serum albumin (HSA)	Improvement of regeneration of cartilage and pain relief in knee OA; anti-inflammatory for severe knee OA	Inhibit the production of pro-inflammatory cytokine in T-cells; induce transcriptional changes of mesenchymal stem cell; up-regulate COX-2, prostaglandin E2 and D2	No serious drug-related AEs	(17, 60–63)
	β-Nerve growth factor (β-NGF) antibody	Modulation of chronic pain	Have effects on nociceptor sensitization	Headache, upper respiratory tract infection and paresthesia	(64–71)
	Interleukin-1 (IL-1) inhibitor	Anti-inflammation	Inhibit the synthesis of proteolytic enzymes, pro-inflammatory cytokines and the degradation of cartilage extracellular matrix	No data available	(72–77)
	Matrix extracellular phosphoglycoprotein (MEPE)	Target subchondral bone remodeling	Regulate subchondral bone mineralization	No serious drug-related AEs	(78, 79)
	Parathyroid hormone (PTH)/ Parathyroid hormone-related protein (PTHrP)	Regulate subchondral bone remodeling and terminal differentiation of articular cartilage	Inhibit chondrocyte hypertrophy, terminal differentiation and degradation	No data available	(80–83)
	Transforming growth factor β (TGF-β) inhibitor	Target subchondral bone remodeling	Inhibit subchondral bone pathology in response to altered mechanical loading	No data available	(84)
	Cholesterol metabolism and inverse agonist of retinoic acid-related orphan receptor alpha (RORα)	Target CH25H-CYP7B1 cholesterol metabolism axis	reduce cartilage destruction and inhibit the up-regulation of MMP3 and MMP13	No data available	(85, 86)