Early diagnosis and targeted intervention based on the pathogenesis of rapidly progressive osteoarthritis of the hip

Table 1 Summary of classification system for rapidly progressive osteoarthritis of the hip

Ref.	Classification	Description	Follow-up period
Irwin and Roberts[6], 1998	Rapid	Chondrolysis for about 18 months followed by bone loss of 10-15 mm/year	> 18 months
	Moderate	Chondrolysis for 18-30 months followed by bone loss at 5-10 mm/year	> 18-30 months
	Delayed	Normal progression for 3-5 years after initial symptoms, then sudden change to rapid or moderate patterns	> 3-5 years
Pivec et al[3], 2013	Type 1	Rapid joint space narrowing, no rapid femoral head dissolution or acetabular bone loss	> 12 months
	Type 2	Severe joint degeneration, rapid progression with femoral head and acetabular destructive changes within 6-18 months	6-18 months
Zazgyva et al[2], 2017	Grade 1	Partial joint space narrowing; no deformation/ascension of the femoral head	> 3.5 years
	Grade 2	Complete disappearance of the joint space; deformed femoral head and acetabulum; femoral head ascension ≤ 0.5 cm above radiological teardrop	> 3.5 years
	Grade 3	Complete disappearance of the joint space; partial osteolysis of the femoral head; femoral head ascension > 0.5 cm above radiological teardrop	> 3.5 years
Yasuda et al[9], 2020	Type 1	Joint space narrowing with no femoral head destruction within 12 months after onset of hip pain	< 12 months
	Type 2	Rapid joint space narrowing and femoral head destruction within 12 months after onset of hip pain	< 12 months

Table 2 Key findings for differential diagnosis of rapidly progressive osteoarthritis of the hip in the early stage

Findings	RPOH	OA	ON	SIF
Pain	Acute and severe, nocturnal	Slow onset, at exertion	At rest and constant	Acute, at rest and exertion
ROM	Normal passive ROM and painful active, weight-bearing ROM	Restricted ROM, Joint stiffness	Joint stiffness less common	Joint stiffness less common
X-ray	Rapid joint space narrowing, lack of osteophytes, and scant/minimal subchondral sclerosis	Gradual joint space narrowing, osteophyte formation, and subchondral sclerosis	Femoral head lucency or sclerosis, and a crescent sign within the femoral head	Fracture on the subchondral area in the femoral head, followed by joint space narrowing
	Femoral head destruction after joint space narrowing
MRI	T1 a subchondral area of low signal intensity	T1: Diffuse low-intensity lesions	T1: Serpentine low-intensity lesions	T1 a band-like hypointense lesion surrounded by a diffuse bone marrow edema pattern
	T2 inhomogeneous high intensity	T2: Diffuse high-intensity lesions	T2: Serpentine high-intensity lesions	T2 a linear pattern of high signal intensity
	Location: The superolateral portion of the femoral head	Location: Weight-bearing portion of femoral head	Location: Any portion and orientation random	Location: Adjacent to the articular surface of the femoral head

RPOH: Rapidly progressive osteoarthritis of the hip; OA: Osteoarthritis of the hip; ON: Osteonecrosis of the femoral head; SIF: Subchondral insufficiency fracture of the femoral head; ROM: Range of hip joint motion; MRI: Magnetic resonance imaging.

Table 3 Potential inhibitors for early intervention to rapidly progressive osteoarthritis of the hip

Agents	Targets	Mechanism	Human disease/animal model	Ref.
Small molecule inhibitors
MCC950	NLRP3	Block ASC oligomerization and inhibit inflammation. Reduce synovitis and cartilage erosion by inhibiting NLRP3 and caspase-1 activation	Mice	[97-100]
VX-765	Caspase-1	Ameliorate the severity and progression of synovitis	Mice	[101,102]
Disulfiram	GSDMD	Inhibits pyroptosis and inflammatory cytokine release in both canonical and noncanonical inflammasome pathways	Mice	[103]
Degrasyn	NLRP3/	Inhibits pyroptosis of synovial macrophages	Mice	[104]
	GSDMD
CY-09	NLRP3	Inhibits cartilage degradation	Rats	[105]
Icariin	NLRP3/	Inhibits inflammation and pyroptosis	Rats	[106]
	Caspase-1
Ursolic acid	NF-κB/	Inhibits cartilage degradation	Rats	[91]
	NLRP3
GYY4137	NF-κB/	Inhibits pyroptosis of synovial macrophages	Mice	[92]
	NLRP3
Loganin	NF-κB/	Inhibits cartilage degradation	Mice	[93]
	Caspase-1
Disease-modifying anti-rheumatic drugs
Chloroquine	The second signal of NLRP3 activation	Inhibit Ca2+-activated K+ channels, which leads to impaired inflammasome activation in THP-1 macrophages Inhibit NLRP3 inflammasome activation	RA/mice	[107,108]
Anakinra	IL-1β receptor antagonist	Inhibit the NLRP3 inflammasome downstream cytokine, IL-1β	RA	[109]
IL-18 binding protein	IL-18 antagonist	Reduces Th17 cells, with the resultant inhibition of osteoclastogenesis, and induces osteoblasts formation	RA/mice	[110]
Tofacitinib	NLRP3	Restore the balance of γδTreg/γδT17 cells by inhibiting NLRP3 inflammasome	RA/mice	[96]

ASC: Apoptosis-associated speck-like protein containing a caspase recruitment domain; NLRP3: Nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3; GSDMD: Gasdermin D; NF-κb: Nuclear factor-κB; IL: Interleukin; RA: Rheumatoid arthritis.