Viscosupplementation for hip osteoarthritis: Does systematic review of patient-reported outcome measures support use?

Alexander J Acuña; Linsen T Samuel; Stacy H Jeong; Ahmed K Emara; Atul F Kamath

doi:10.1016/j.jor.2020.03.016

. 2020 Mar 25;21:137–149. doi: 10.1016/j.jor.2020.03.016

Viscosupplementation for hip osteoarthritis: Does systematic review of patient-reported outcome measures support use?^☆

Alexander J Acuña ¹, Linsen T Samuel ¹, Stacy H Jeong ¹, Ahmed K Emara ¹, Atul F Kamath ^1,^∗

PMCID: PMC7114596 PMID: 32255995

Abstract

Introduction

Osteoarthritis of the hip is one of the leading causes of disability worldwide. There is lack of agreement among providers and governing agencies regarding the efficacy of hyaluronic acid (HA) for the management of hip osteoarthritis (OA). Therefore, the purpose of this systematic review was to determine how HA administration impacts 1) patient reported outcome measures (PROMs) and 2) rates of conversion to THA.

Methods

The PubMed, EBSCO host, and Google Scholar electronic databases were queried for all studies published between January 1st, 2000 and January 1st, 2020 that reported on outcomes following HA administration for treatment of hip OA. The following keywords were implemented with AND and OR Boolean operators: “hip”; “osteoarthritis”; “arthritis”; “viscosupplementation”; “hyaluronic acid.” Our final analysis included 39 studies and reported on a total of 5,864 patients receiving injections of HA.

Results

All studies reporting on visual analog scale (VAS), patient global assessment, and total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores demonstrated improvements following HA administration. For the Lequesne Index (LI), WOMAC pain, WOMAC function, and Harris Hip Score (HHS) values, a majority of studies reported that HA would prove beneficial, with one analysis suggesting a lack of improvement. There was inconsistent evidence across studies regarding the effectiveness of HA compared to other intra-articular injections. The formulation of the administered viscosupplementation did not appear to influence outcomes. Furthermore, rates of conversion to THA were relatively low when evaluating 1- to 4-year follow-up intervals.

Discussion

Non-comparative studies consistently demonstrated that HA can achieve satisfactory pain reduction and functional improvement. However, there was not enough evidence in the current literature regarding whether HA is superior to placebo or other types of intra-articular injections. Future studies should continue to compare HA to other treatment modalities in randomized controlled trials with larger sample sizes.

Keywords: Hyaluronic acid, Viscosupplementation, Hip osteoarthritis (OA), Pain, Function, Systematic review

1. Introduction

With an estimated prevalence of over 27 million individuals, osteoarthritis (OA) of the hip continues to be a significant source of disability among Americans.¹^,² The incidence of this degenerative disorder is expected to rise given the ongoing obesity epidemic and progressively aging population.3, 4, 5 Although total hip arthroplasty (THA) is effective in reducing pain and restoring function among those with hip OA, the high procedural volume of THA only further contributes to the substantial financial burden associated with OA management.6, 7, 8 Therefore, providers may seek non-surgical management strategies for hip OA. The use of intra-articular injections of hyaluronic acid (HA) has subsequently become an increasingly popular treatment choice.

A large component of normal synovial fluid, hyaluronic acid typically exerts a protective effect on the articular cartilage through maintaining lubrication of the joint and subsequently reducing the effects of mechanical forces.⁹ Additionally, multiple studies have shown that administration of HA results in anti-inflammatory effects, including the reduction of synovial inflammation and the downregulation of inflammatory cytokines and proteases.10, 11, 12, 13Although multiple systematic reviews have previously demonstrated positive outcomes following treatment with HA,14, 15, 16 the American Academy of Orthopaedic Surgeons (AAOS) does not support the routine use of intra-articular HA in its guidelines for management of hip OA.¹⁷ Therefore, there is a continued need for comprehensive reviews of the literature in order to determine if HA injections should be supported in routine clinical use.¹⁸

Osteoarthritis of the hip is one of the leading causes of disability worldwide. Although some studies have shown that administration of hyaluronic acid can provide therapeutic benefits to those suffering from hip OA, there is a lack of agreement among providers and governing agencies regarding the efficacy of HA injections in the hip. Therefore, the purpose of this systematic review was to determine how HA administration impacts 1) patient reported outcome measures (PROMs) and 2) rates of conversion to THA.

2. Methods

2.1. Literature search

The PubMed, EBSCO host, and Google Scholar electronic databases were queried for all studies published between January 1st, 2000 and January 1st, 2020 that reported on outcomes following HA administration for the treatment of hip OA. The following keywords were implemented with AND and OR Boolean operators: “hip”; “osteoarthritis”; “arthritis”; “viscosupplementation”; “hyaluronic acid.”

Studies were included if they met the following inclusion criteria: 1) full-text, English manuscripts were available, 2) the study reported on viscosupplementation for patients with hip OA, 3) patient reported outcome measures or rates of conversion to THA were reported, 4) the patient population suffered from OA of the hip. Exclusion criteria consisted of the following: 1) single or double case reports, 2) systematic reviews (bibliography of each systematic review was reviewed manually), 3) cadaveric studies, 4) studies that reported on patients primarily with rheumatoid arthritis, and 5) studies reporting on outcomes outside of PROMs and conversion rates to THA.

2.2. Study selection

The initial query yielded 362 studies. Following the removal of 129 duplicates, 233 studies remained for consideration. The abstracts and titles of each study were then reviewed to determine if they met the predetermined inclusion criteria. A total of 45 full-text manuscripts were then considered following this stage in the selection process. Following a review of the entire manuscript, 6 articles were further eliminated. This resulted in 39 studies being considered further. A review of each study's reference list did not yield additional articles for consideration (Fig. 1). Therefore, our final analysis included 39 studies which reported on a total of 5,864 patients receiving injections of HA (Table 1).

Fig. 1 — PRISMA diagram demonstrating article selection process.

Table 1.

Included studies reporting on outcomes following viscosupplementation.

Study	Summary	HA Dosing	Cohort Size	Arthritis Grade	Follow-Up Period	Variables
De Lucia et al. 2019⁴⁸	HMW-HA vs. MMW-HA vs. Controls	HMW (x3) vs. MMW (x3)	HMW: n = 43, MMW: n = 79, Controls: n = 20	KL II-IV	1-month 6-months 12-months 24-months	VAS WOMAC Total, Pain, Function
Brander et al. 2019⁴⁹	HA vs. NS	Hylan G-F 20 (x1)	HA: n = 182; Saline: n = 175	KL II-III	26-weeks	WOMAC Total Patient Global Self-Assessment
Clementi et al. 2018¹⁹	UHMW-HA vs. MMW-HA	Fermathron S (1x), Hyalubrix 60 (1x)	UHMW: n = 23; MMW: n = 27	KL III	1-month 3-month 6-month 12-month	Lequesne Index VAS WOMAC Pain, Function
Suppan et al. 2017⁵⁴	HA vs. HA	GO-ON (1x vs. 3x)	Single: n = 63; Triple: n = 64	KL I-III	3-months	WOMAC Total
Doria et al. 2017³⁵	HA vs. PRP	Hyalubrix (x3)	HA: n = 40; PRP: n = 40	KL 0-II	6-months 12-months	WOMAC Pain, Function VAS HHS
Mauro et al. 2017²⁰	HA (Hyalubrix) + exercise therapy	Hyalubrix (x3)	n = 40	KL II-IV	10-weeks	VAS Lequesne Index
Migliore et al. 2017²¹	HA	HyalOne/Hyalubrix (x1)	n = 1,022	KL I-IV	Every 6-months for 7-years	Lequesne Index VAS Patient Global Self-Assessment
Abate et al. 2017²²	LMW + HMW-HA vs. HMW-HA	LMW + HMW (x1), HMW (x1)	LMW + HMW: n = 20; HMW: n = 20	KL II-IV	3-months 6-months	Lequesne Index HHS VAS
Eymard et al. 2017⁵³	HA	HAnox-M-XL (1x)	n = 90	KL I-IV	3-months	WOMAC Pain, Function Patient Global Self-Assessment
Di Sante et al. 2016³⁶	HA vs. PRP	Na-HA (x3)	HA: n = 22; PRP: n = 21	KL II-III	1-month 4-months	VAS WOMAC Pain, Function
Dallari et al. 2016³⁷	HA vs. PRP vs. HA + PRP	Hyalubrix (x3)	HA: n = 36; PRP: n = 44; PRP + HA: n = 31	KL I-IV	2-months 6-months 12-months	VAS HHS WOMAC Total
Battaglia et al. 2013³⁸	HA vs. PRP	Hyalubrix (x3)	HA: n = 50; PRP: n = 50	KL II-IV	1-month 3-month 6-month 12-month	VAS HHS
Migliore et al. 2012⁶¹	HA	HyalOne (x1)	n = 176	KL I-IV	24-months 48-months	THA Rates
Migliore et al. 2012⁶²	HA	Hylan G-F 20 (x1)	n = 224	KL I-IV	12-months 24-months 5-years	THA Rates
Migliore et al. 2011²³	HA	HyalOne (x1)	n = 120	KL I-IV	3-month intervals up to 18-months	VAS Lequesne Index
Atchia et al. 2011⁵⁰	HA vs. No Injection vs. NS vs. Corticosteroid	Durolane (x1)	HA: n = 19; NS: n = 19; Corticosteroid: n = 20; No Injection: n = 20	Croft 1–2 or 3-4	1-week 1-month 2-months	WOMAC Pain, Function
Spitzer et al. 2010⁵¹	HA vs. Methylprednisolone	Hylan G-F 20 (x2)	HA: n = 150; MPA: n = 155	KL II-III	1-month 2-months 3-months 4-months 5-months 26-weeks	WOMAC Total, Pain, Function Patient Global Self-Assessment
Eyigor et al. 2010²⁴	HA	Adant (x3)	n = 21	KL III-IV	1-month 3-month 6-months	VAS Lequesne Index
Migliore et al. 2009²⁵	HA	Hylan G-F 20 (x1)	n = 78	KL I-IV	3-months 6-months 9-months 12-months	VAS Lequesne Index
Dıraçoğlu et al. 2009³⁹	HA	N/A (x3)	n = 19	KL I-II	1-month	VAS WOMAC Total, Pain, Function
Conrozier et al. 2009²⁶	HA	NASHA (x1)	n = 34	KL I-IV	Mean: 159 days (range: 60–180)	Patient Global Self-Assessment VAS WOMAC Pain, Function Lequesne Index
Richette et al. 2009⁴⁰	HA vs. Placebo	Adant (x1)	HA: n = 42; Placebo: n = 43	KL II-III	3-months	VAS WOMAC Total, Pain, Function Patient Global Self-Assessment
Migliore et al. 2009²⁷	HA vs. Anaesthetic	Hyalubrix (x1)	HA: n = 22; Anaesthetic: n = 20	KL II-IV	3-months 6-months	VAS Lequesne Index Patient Global Self-Assessment
Migliore et al. 2008²⁸	HA	Hylan G-F 20 (x1-x3)	n = 250	KL II-III	3-months 6-months 9-months 12-months	VAS Lequesne Index Patient Global Self-Assessment
Van Den Bekerom et al. 2008⁴¹	HA Formulations (Adant, Synocrom, Synvisc)	Adant (x1), Synocrom (x1), Synvisc (x1)	Adant: n = 91; Synocrom: n = 20; Synvisc: n = 15	N/A	6-weeks	VAS HHS THA rates
Gaston et al. 2007⁵⁵	HA	Suplasyn (x3)	n = 15	Mean: 2.7 ± 0.88	3-months 6-months	HHS
Conrozier et al. 2006⁴²	HA	Hylan G-F 20 (x1/x2)	n = 56	KL II-III	3-months	WOMAC Pain, Function Patient Global Self-Assessment VAS
Van Den Bekerom et al. 2006⁴³	HA Formulations	Orthovisc (x1-x3), Synvisc (x1-x3), Fermatron (x1-x3)	n = 60	N/A	6-weeks	VAS THA rates
Migliore et al. 2005²⁹	HA	Hylan G-F 20 (x1)	n = 30	KL I-III	2-months 6-months	Lequesne Index VAS
Qvistgaard et al. 2006⁴⁴	HA vs. NS vs. Corticosteroid	Hyalgan (x3)	HA: n = 33; NS: n = 36; Corticosteroid: n = 32	KL I-II or III-IV	2-weeks 4-weeks 3-months	VAS
Migliore et al. 2005³⁰	HA	Hyalgan (x2)	n = 14	KL II-IV	3-months 6-months 9-months 12-months	VAS Lequesne Index Patient Global Self-Assessment
Pourbagher et al. 2005⁴⁵	HA	Na-hyaluronate (x3)	n = 10	Hartofilakidis I-II	2-months 4-months 6-months	VAS WOMAC Total
Tikiz et al. 2005³¹	HA Formulations	Hylan G-F 20 (x3), Na-hyaluronate (x3)	Hylan G-F 20 (n = 18) vs. Na-Hyaluronte (n = 25)	KL 1-III	1-month 3-months 6-months	VAS WOMAC Total Lequesne Index
Migliore et al. 2005³²	HA	Hylan G-F 20 (x1)	n = 12	KL I-II or III-IV	1-month 3-month	VAS Lequesne Index
Caglar-Yagci et al. 2005³³	HA	Hylan G-F 20 (x3)	n = 14	KL I-III	1-month 3-months	VAS Lequesne Index
Berg et al. 2004⁵²	HA	NASHA (x1)	n = 31	KL II-III	2-weeks 3-months	WOMAC Pain, Function Patient Global Self-Assessment
Conrozier et al. 2003⁴⁶	HA	Hylan G-F 20 (x1/x2)	n = 57	KL II-III	3-months	VAS WOMAC Total, Pain, Function Patient Global Self-Assessment
Vad et al. 2003⁴⁷	HA	Hylan G-F 20 (x3)	n = 22	N/A	12-months	VAS
Brocq et al. 2002³⁴	HA	Hylan G-F 20 (x1/x2)	n = 22	KL I-III	1-week 1-months 2-months 3-months 6-months	VAS Lequesne Index

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HA: Hyaluronic Acid; PRP: Platelet-Rich Plasma; NS: Normal Saline; UHMW: Ultra High Molecular Weight; HMW: High Molecular Weight; MMW: Medium Molecular Weight; LMW: Low Molecular Weight; THA: total hip arthroplasty; VAS: visual analog scale; HHS: Harris Hip Score; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; N/A: Information Not Available; KL: Kellgren-Lawrence.

3. Results

3.1. Lequesne Index

A total of 16 studies utilized the Lequesne Index (LI) to report outcomes following viscosupplementation.19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 Of these, 15 analyses reported decreases in LI scores following the administration of HA, with 13 studies reporting significant reductions at their respective time frames21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 (Table 2). Conversely, Conronzier et al. was the only included study to report no difference in LI values following HA administration (8.9 ± 3 vs. 6.9 ± 0.5; p = 0.12)²⁶.

Table 2.

Changes in lequesne index reported among hyaluronic acid cohorts.

Study/Interval	Baseline		Follow-Up		p-value
Study/Interval	Mean	SD	Mean	SD	p-value
1-week
Brocq et al. 2002³⁴	11.6	4.1	6.9	4.9	–
1-month
Clementi et al. 2018¹⁹
UHMW	11.5	4.4	9.8	4.4	–
MMW	12.5	4.1	10.6	3.7	–
Eyigor et al. 2010²⁴	15.1	–	11.24	–	<0.001
Tikiz et al. 2005³¹
Na-Hyaluronate	11.4	4.6	5.9	4.8	<0.001
Hylan G-F 20	11.8	3.3	7.1	4.5	<0.05
Migliore et al. 2005³²	14.817	–	12.167	–	<0.05
Caglar-Yagci et al. 2005³³	12.57	0.55	9	0.68	<0.001
Brocq et al. 2002³⁴	11.6	4.1	6.9	4.9	–
2-months
Brocq et al. 2002³⁴	11.6	4.1	5.9	5.2	–
Migliore et al. 2005²⁹	11.59	4.41	7.23	3.95	<0.001
10-weeks
Mauro et al. 2017²⁰	12.9	4.2164	5.5	2.5731	–
3-months
Clementi et al. 2018¹⁹
UHMW	11.5	4.4	9.9	3.3	–
MMW	12.5	4.1	9.3	3.5	–
Abate et al. 2017²²
HI LOW Hybrid	5.5	3.1	4.6	2.6	<0.001
HMW	5.4	3.3	5.1	3	0.002
Eyigor et al. 2010²⁴	15.1	–	11.67	–	<0.001
Migliore et al. 2009²⁵	7.84	–	4.38	–	<0.0005
Migliore et al. 2009²⁷	7.09	3.78	5.15	5.15	<0.001
Miglore et al. 2005³²	14.817	–	11.708	–	<0.05
Tikiz et al. 2005³¹
Na-Hyaluronate	11.4	4.6	6.2	4.8	<0.001
Hylan G-F 20	11.8	3.3	6.3	4.3	<0.001
Migliore et al. 2005³⁰	11.3	5.7	5.9	4.4	<0.05
Caglar-Yagci et al. 2005³³	12.57	0.55	9	0.68	<0.001
Brocq et al. 2002³⁴	11.6	4.1	5.7	4.2	–
159 days (range: 60–180)
Conrozier et al. 2009²⁶	8.9	3	6.9	0.5	0.12
6-months
Clementi et al. 2018¹⁹
UHMW	11.5	4.4	9.7	3	–
MMW	12.5	4.1	9.6	3.4	–
Abate et al. 2017²²
HI LOW Hybrid	5.5	3.1	3.9	2.5	<0.001
HMW	5.4	3.3	4.9	2.9	0.002
Eyigor et al. 2010²⁴	15.1		12.48		<0.001
Migliore et al. 2009²⁵	7.84	–	5	–	<0.0005
Migliore et al., 2009	7.09	3.78	3.94	2.58	<0.001
Migliore et al. 2005²⁹	11.59	4.41	6.15	4.45	<0.001
Migliore et al. 2005³⁰	11.3	5.7	6.9	5.3	<0.05
Tikiz et al. 2005³¹
UHMW	11.5	4.4	6.2	5.8	<0.001
MMW	12.5	4.1	5.9	5.4	<0.001
Brocq et al. 2002³⁴	11.6	4.1	5.7	4.2	–
9-months
Migliore et al. 2009²⁵	7.84	–	4.38	–	<0.0005
Migliore et al. 2005³⁰	11.3	5.7	8	7.5	<0.05
12-months
Clementi et al. 2018¹⁹
UHMW	11.5	4.4	9.8	3.3	–
MMW	12.5	4.1	9.5	3.3	–
Migliore et al. 2009²⁵	7.84	–	4.12	–	<0.0005
Migliore et al. 2005³⁰	11.3	5.7	6.9	6.1	<0.05

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UHMW: Ultra High Molecular Weight; HMW: High Molecular Weight; MMW: Medium Molecular Weight; LMW: Low Molecular Weight; VAS: visual analog scale; HHS: Harris Hip Score; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; N/A: Information Not Available; KL: Kellgren-Lawrence.

In addition to the granular data available in Table 2, Migliore et al. reported significant reductions in LI values at 3-, 6-, 9-, and 12-month follow-up intervals for HA patients (p < 0.05) in both 2008²⁸ and 2009.²⁵ The authors later demonstrated significant improvements at all previously reported time points as well as at 18-months (p < 0.001), with 42% of included patients reporting an improved score at final follow-up.²³ Furthermore, Migliore et al. found that patients treated with HA continued to demonstrate reductions in Lequesne Index scores up to 7-year follow-up.²¹

No differences in LI scores were found when comparing different HA formulations (Table 3). Migliore et al. was the only study to evaluate the efficacy of HA compared to another type of intra-articular injection.²⁷ The authors found significantly lower LI scores for the HA cohort at all follow-up intervals (Table 4).

Table 3.

Comparisons of HA formulations/dosing schedules.

	Study	Comparison				Follow-Up	p-values
Lequesne Index	Tikiz et al.³¹	Na-Hyaluronate		Hylan G-F 20		1-month 3-months 6-months	0.34 0.84 0.89
	Abate et al.²²	HMW-HA		Combined HMW and LMW HA		6-months	>0.05
	Clementi et al.¹⁹	MMW-HA		UHMW-HA		1-month 3-months 6-months 12-months	0.4 0.5 0.8 0.7
VAS	Tikiz et al.³¹	Na-Hyaluronate		Hylan G-F 20		1-month 3-months 6-months	0.78 0.96 0.18
	Van Den Bekerom et al.⁴¹	Synvisc	Adant		Synocrom	6-weeks	>0.05
	Abate et al.²²	HMW-HA		Combined HMW and LMW HA		6-months	<0.02
	Clementi et al.¹⁹	MMW-HA		UHMW-HA		1-month 3-months 6-months 12-months	0.7 0.6 0.6 0.9
WOMAC Total	Suppan et al.⁵⁴	GO-ON x1		GO-ON x3		3-months	0.889
WOMAC Total	Clementi et al.¹⁹	MMW-HA		UHMW-HA		1-month 3-months 6-months 12-months	0.9 0.9 0.8 0.9
HHS	Abate et al.²²	HMW-HA		Combined HMW and LMW HA		6-months	<0.001
HHS	Van Den Bekerom et al.⁴¹	Synvisc	Adant		Synocrom	6-weeks	>0.05

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Table 4.

Efficacy of hyaluronic acid compared to other types of intra-articular injections.

Variable	Study	Comparison					Follow-Up	HA Cohort (Mean ± SD)	Comparison Cohort (Mean ± SD)	p-value
Lequesne Index	Migliore et al.²⁷	Mepivacaine					3-months 6-months	5.15 ± 5.15 3.94 ± 2.58	6.53 ± 4.33 6.41 ± 4.14	<0.001 <0.05
VAS	Dallari et al.³⁷	PRP					2-month 6-month 12-month	38 44 42	23 21 24	0.026 0.0005 0.002
	Battaglia et al.³⁸						1-month 3-months 6-months 12-months	3.58 3.80 4.04 4.59	3.72 3.80 4.29 4.75	>0.05 >0.05 >0.05 >0.05
	Di Sante et al.³⁶						4-weeks 16-weeks	5.27 ± 1.6 3.63 ± 2.1	4.73 ± 3.4 6.36 ± 2.1	N/A 0.0004
	Qvistgaarde et al.⁴⁴	Placebo					2-weeks 4-weeks 3-months	N/A		0.13
		Corticosteroid					2-weeks 4-weeks 3-months	N/A		0.069 0.14 0.57
	Richette et al.⁴⁰	Placebo					3-months	−7.8 ± 24.9^a	−9.1 ± 27.4^a	>0.05
	Migliore et al.²⁷	Mepivacaine					3-months 6-months	4.3 ± 2.58 4.5 ± 1.96	4.5 ± 2.63 5.0 ± 2.41	<0.05 <0.05
WOMAC - Pain	Di Sante et al.³⁶	PRP					4-weeks 16-weeks	29.6 ± 13.4 19.9 ± 11.4	44.27 ± 28.8 53.47 ± 2.3	N/A
	Richette et al.⁴⁰	Placebo					3-months	−8.6 ± 22.3^a	−7.5 ± 24.6^a	>0.05
	Spitzer et al.⁵¹	Methylprednisolone acetate					26-weeks	−16.62 ± 2.40^a	−13.59 ± 2.38	0.8496
	Brander et al.⁴⁹	Placebo					4-weeks 8-weeks 12-weeks 16-weeks 20-weeks 26-weeks	−1.83 ± 0.15† −2.27 ± 0.19† −2.12 ± 0.18† −2.42 ± 0.20† −2.28 ± 0.19† −2.23 ± 0.21†	−1.95 ± 0.16† −2.36 ± 0.19† −2.44 ± 0.19† −2.32 ± 0.20† −2.20 ± 0.19† −2.30 ± 0.22†	0.5753 0.7344 0.2140 0.7180 0.7817 0.8352
	Atchia et al.⁵⁰	Methylprednisolone acetate	Saline		No-Injection		1-week 1-month 2-months	N/A		0.003‡
WOMAC - Function	Di Sante et al.³⁶	PRP					4-weeks 16-weeks	39.13 ± 17.2 28.39 ± 17.2	49.13 ± 29.1 50.80 ± 22.8	N/A
	Richette et al.⁴⁰	Placebo					3-months	−6.7 ± 22.7^a	−5.7 ± 19.9^a	>0.05
	Spitzer et al.⁵¹	Methylprednisolone acetate					4-weeks 26-weeks	−18.19 ± 1.79^a −13.80 ± 2.32^a	−26.57 ± 1.73^a −11.53 ± 2.30^a	0.0005 0.4751
	Brander et al.⁴⁹	Placebo					4-weeks 8-weeks 12-weeks 16-weeks 20-weeks 26-weeks	−1.81 ± 0.16† −2.14 ± 0.18† −1.94 ± 0.19† −2.27 ± 0.2† −2.05 ± 0.19† −2.09 ± 0.21†	−1.83 ± 0.16† −2.23 ± 0.19† −2.28 ± 0.19† −2.17 ± 0.20† −2.01 ± 0.20† −2.06 ± 0.17†	0.9304 0.7226 0.1916 0.7394 0.8658 0.8753
	Atchia et al.⁵⁰	Methylprednisolone acetate		Saline		No-Injection	1-week 1-month 2-months	N/A		0.009‡
WOMAC - Total	Dallari et al.³⁷	PRP					2-month 6-month 12-month	59 59 –	73 72 –	0.009 0.009 >0.05
	Spitzer et al.	Methylprednisolone acetate					4-weeks 26-weeks	−18.18 ± 1.75^a −14.70 ± 2.32^a	−26.98 ± 1.69^a −12.00 ± 2.29^a	0.0002 0.3959
	Richette et al.⁴⁰	Placebo					3-months	−6.2 ± 21.3	−6.5 ± 20.2	>0.05
HHS	Dallari et al.³⁷	PRP					2-month 6-month 12-month	N/A		>0.05 >0.05 >0.05
	Battaglia et al.³⁸	PRP					1-month 3-months 6-months 12-months	78.02 77.23 75.79 72.55	73.72 72.90 70.23 65.73	>0.05 >0.05 >0.05 >0.05
	Doria et al.³⁵	PRP					6-months 12-months	75 ± 11.5 78 ± 11.3	74 ± 12.3 75 ± 11.4	N/A
Patient Global Self-Assessment	Brander et al.⁴⁹	Placebo					4-weeks 8-weeks 12-weeks 16-weeks 20-weeks 26-weeks	−1.68 ± 0.16† −2.16 ± 0.19† −1.84 ± 0.19† −2.28 ± 0.20† −1.97 ± 0.21† −2.07 ± 0.22†	−1.89 ± 0.17† −2.31 ± 0.20† −2.19 ± 0.19† −2.09 ± 0.21† −1.78 ± 0.21† −2.11 ± 0.23†	0.3664 0.5852 0.1944 0.5013 0.5143 0.9193
	Richette et al.⁴⁰	Placebo					3-months	−7.0 ± 24.9^a	−5.4 ± 27.2^a	>0.05
	Migliore et al.²⁷	Mepivacaine					3-months 6-months	4.5 ± 2.31 4.0 ± 2.06	4.7 ± 2.33 4.9 ± 2.01	>0.05 >0.05
	Spitzer et al.⁵¹	Methylprednisolone acetate					4-weeks 26-weeks	−17.11 ± 1.94^a −16.67 ± 2.25^a	−26.10 ± 1.88^a −12.71 ± 2.51^a	0.0006 0.2537

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Values reported as Standard Error of the Mean (SEM). HA: Hyaluronic Acid; PRP: Platelet-Rich Plasma; NS: Normal Saline; UHMW: Ultra High Molecular Weight; HMW: High Molecular Weight; MMW: Medium Molecular Weight; LMW: Low Molecular Weight; THA: total hip arthroplasty; VAS: visual analog scale; HHS: Harris Hip Score; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; N/A: Information Not Available; KL: Kellgren-Lawrence; SD: standard deviation.

3.2. Visual analog scale

A visual analog scale (VAS) measured patient reported pain in 29 studies.19, 20, 21, 22, 23, 24^,26, 27, 28, 29, 30, 31^,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 All studies indicated that VAS scores were reduced following HA administration. Specifically, 19 studies reported significant reductions at their respective follow-up periods20, 21, 22^,24, 25, 26^,28, 29, 30, 31, 32, 33^,³⁵^,37, 38, 39^,⁴¹^,⁴⁶^,⁴⁸ (Table 5).

Table 5.

Visual analog scale pain scale scores following viscosupplementation.

Study/Interval	Baseline		Follow-Up		p-value
1-month	Mean	SD	Mean	SD	p-value
Clementi et al. 2018¹⁹
UHMW	6.4	1.7	5.1	1.6	–
MMW	6.3	2.1	4.9	1.8	–
Di Sante et al. 2016³⁶	6.32	1.7	5.27	1.6	<0.01
Battaglia et al. 2013³⁸	5.97	–	3.58	–
Eyigor et al. 2010²⁴	7.52	–	2.81	–	<0.001
Dıraçoğlu et al. 2009³⁹	6.88	0.99	3.12	1.22	<0.001
Tikiz et al. 2005³¹
Na-Hyaluronate	7.2	1.5	4.1	2.6	<0.001
Hylan G-F 20	6.7	1.7	4.4	2.3	<0.001
Migliore et al. 2005³²	7.81	–	5.87	–	<0.05
Caglar-Yagci et al. 2005³³	77.35	13.74	48.92	21.62	<0.001
Brocq et al. 2002³⁴	55.4	14.9	30.7	22.2	–
6-weeks
Van Den Bekerom et al. 2008⁴¹
Adant®	51	23	39	27	<0.0001
Synocrom®	43	22	29	23	<0.02
Synvisc®	47	26	30	29	>0.05
Van Den Bekerom et al. 2006⁴³	66.3	–	49.3	–
2-months
Miglore et al. 2005²⁹	6.85	2.08	4.04	2.56	<0.001
Pourbagher et al. 2005⁴⁵	8.3	0.56	4.75	0.64	–
Brocq et al. 2002³⁴	55.4	14.9	30.5	24.8	–
10-weeks
Mauro et al. 2017²⁰	6.18	2.537	1.31	1.478	<0.05
3-months
Clementi et al. 2018¹⁹
UHMW	6.4	1.7	4.7	1.3	–
MMW	6.3	2.1	4.5	1.5	–
Abate et al. 2017²²
HI LOW Hybrid	4.5	1	3.3	0.8	<0.001
HMW	4.4	1.5	3.5	1.3	<0.001
Battaglia et al. 2013³⁸	5.97	–	3.8	–	–
Eyigor et al. 2010²⁴	7.52	–	2.9	–	<0.001
Migliore et al. 2009²⁵	6	–	3.72	–	<0.0005
Migliore et al. 2009²⁷	6.4	1.94	4.3	2.58	–
Migliore et al. 2005³⁰	6.5	2.1	4.4	2.1	<0.05
Tikiz et al. 2005³¹
Na-Hyaluronate	7.2	1.5	4.6	2.5	<0.001
Hylan G-F 20	6.7	1.7	4.7	2.7	<0.001
Migliore et al. 2005³²	7.81	–	5.25	–	0.004
Caglar-Yagci et al. 2005³³	77.35	13.74	28.57	19.87	<0.001
Conrozier et al. 2003⁴⁶	69.3	11.9	39.5	29.5	<0.0001
Brocq et al. 2002³⁴	55.4	14.9	30.4	22.2	–
4-months
Di Sante et al. 2016³⁶	6.32	1.7	3.63	2.1	–
Pourbagher et al. 2005⁴⁵	8.3	0.56	20.9	6.37	–
159 days (range: 60–180)
Conrozier et al. 2009²⁶	51.9	20.8	31.1	4.1	0.0001
6-months
Clementi et al. 2018¹⁹
UHMW	6.4	1.7	5	1.5	–
MMW	6.3	2.1	4.7	1.3	–
Doria et al. 2017³⁵	7.8	1.9	6.3	2.9	0.0007
Abate et al. 2017²²
HI LOW Hybrid	4.5	1	2.5	0.8	<0.001
HMW	4.4	1.5	3.2	1.2	<0.001
Battaglia et al. 2013³⁸	5.97	–	4.04	–	–
Eyigor et al. 2010²⁴	7.52	–	4.52	–	–
Migliore et al. 2009²⁵	6	–	4.17	–	<0.0005
Migliore et al. 2009²⁷	6.4	1.94	4.5	1.96	–
Miglore et al. 2005²⁹	6.85	2.08	4.26	3.04	<0.001
Migliore et al. 2005³⁰	6.5	2.1	5	2.3	<0.05
Pourbagher et al. 2005⁴⁵	8.3	0.56	4.4	0.7	–
Tikiz et al. 2005³¹
Na-Hyaluronate	7.2	1.5	4.6	2.5	<0.001
Hylan G-F 20	6.7	1.7	3.4	3	<0.001
Brocq et al. 2002³⁴	55.4	14.9	24.7	17.1	–
9-months
Migliore et al. 2009²⁵	6	–	3.88	–	<0.0005
Migliore et al. 2005³⁰	6.5	2.1	4.3	3.2	<0.05
12-months
Clementi et al. 2018¹⁹
UHMW	6.4	1.7	4.8	1.6	–
MMW	6.3	2.1	4.9	1.6	–
Doria et al. 2017³⁵	7.8	1.9	6.3	2.9	0.00654
Battaglia et al. 2013³⁸	5.97	–	4.59	–	–
Migliore et al. 2009²⁵	6	–	3.63	–	<0.0005
Migliore et al. 2005³⁰	6.5	2.1	3.5	3	<0.05
Vad et al. 2003⁴⁷	8.7	–	2.3	–	–

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UHMW: Ultra High Molecular Weight; HMW: High Molecular Weight; MMW: Medium Molecular Weight; LMW: Low Molecular Weight.

Outside of the data reported in Table 5, Migliore et al. found significant reductions in VAS scores at all follow-up periods (all p-values <0.05)²⁸. Similarly, Migliore et al.²¹ found significant reductions in VAS scores up to 84-months follow-up (p < 0.05). This finding was demonstrated even when the authors stratified their patient population based on age, BMI, and gender. These authors later found that 83.3% of patients had at least a 30% reduction in their pain at 12-month follow-up.²³ Furthermore, Conrozier et al. reported pain reduction ≥50% in 51.8% of their patients receiving HA injections.⁴²

There was mixed evidence regarding which HA formulation was most effective (Table 3). Similarly, there was a lack of consensus among included studies regarding whether HA yielded superior results compared to other types of injections (Table 4).

3.3. WOMAC

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was implemented by 18 included studies.¹⁹^,²⁶^,³¹^,35, 36, 37^,³⁹^,⁴⁰^,⁴²^,⁴⁵^,⁴⁶^,48, 49, 50, 51, 52, 53, 54 A large majority of included analyses demonstrated improvements in WOMAC values following viscosupplementation.

Among these, the pain (WOMAC-A) and function (WOMAC-C) subscales were reported on by 13 analyses.²⁶^,³⁵^,³⁶^,³⁹^,⁴⁰^,⁴²^,⁴⁶^,48, 49, 50, 51, 52, 53 In addition to the extractable data available in Table 6 and Table 7, Brander et al. found a significant improvement in WOMAC pain and function scores at 4-, 8-, 12-, 16-, 20-, and 26- week follow-up (all p-values <0.001)⁴⁹. Similarly, Richette et al. found reductions in pain (mean change: −8.6 ± 22.3) and function (mean change: −6.7 ± 22.7) values for their HA cohort at 3-month follow-up. Atchia et al. remained the only analysis that did not report significant reductions in WOMAC pain and function values following viscosupplementation.⁵⁰

Table 6.

Reported WOMAC pain values.

Study/Interval	Baseline		Follow-Up		p-value
Study/Interval	Mean	SD	Mean	SD	p-value
2-weeks
Berg et al. 2004⁵²	11.2	2.5	4.8	–	<0.0001
1-month
Di Sante et al. 2016³⁶	42.36	20.5	29.6	13.4	>0.05
Dıraçoğlu et al. 2009³⁹	5.88	0.93	4.21	0.81	<0.001
3-months
Eymard et al. 2017⁵³	26	–	16.5	–	<0.0001
Conrozier et al. 2006⁴²	53.7	17.2	34.9	24.1	–
Berg et al. 2004⁵²	11.2	2.5	5.5	–	<0.0001
Conronzier et al. 2003⁴⁶	53.7	17.2	34.9	27.1	<0.0001
4-months
Di Sante et al. 2016³⁶	42.36	20.5	19.9	11.4	<0.01
159 Days (Range: 60–120)
Conrozier et al. 2009⁴⁰	209	105	153.7	19.4	0.043
6-months
Doria et al. 2017³⁵	24	1.9	9.7	4.5	0.00063
26-weeks
Brander et al. 2019⁴⁹	6.35	0.07*	–	–	<0.0001
Spitzer et al. 2010⁵¹	63.06	1.14	–	–	<0.0001
12-months
Doria et al. 2017³⁵	24	1.9	9	5.6	0.00591

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*Values reported as Standard Error of the Mean (SEM). WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; SD: standard deviation.

Table 7.

WOMAC function values following hyaluronic acid administration.

Study/Interval	Baseline		Follow-Up		p-value
Study/Interval	Mean	SD	Mean	SD	p-value
2-weeks
Berg et al. 2004⁵²	35.8	9.5	10.9	–	<0.05
1-month
Di Sante et al. 2016³⁶	57.65	26.2	47.69	21.2	>0.05
Atchia et al. 2011⁵⁰
Dıraçoğlu et al. 2009³⁹	6.23	0.78	4.57	0.63	<0.001
3-months
Eymard et al. 2017⁵³	84	–	58	–	<0.0001
Conrozier et al. 2006⁴²	50.8	20.3	34.4	26.9	–
Berg et al. 2004⁵²	35.8	9.5	15.9	–	<0.05
Conronzier et al. 2003⁴⁶	54.2	23.2	34.6	27.2	<0.001
4-months
Di Sante et al. 2016³⁶	57.65	26.2	32.91	20.6	<0.01
159 days (Range: 60–180)
Conrozier et al. 2009²⁶	89	57	67.4	8.3	0.019
6-months
Doria et al. 2017³⁵	28.5	2.5	11.3	4.5	–
26-weeks
Spitzer et al. 2010⁵¹	64.42	1.40	–	–	<0.0001
12-months
Doria et al. 2017³⁵	28.5	2.5	10.9	4.2	–

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WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; SD: standard deviation.

Total WOMAC scores were utilized by 10 studies^{19,31,37,39,40,45,46,51,54 48}. All analyses demonstrated improvements in total WOMAC values, with 8 analyses reporting significant improvements following HA administration³¹^,³⁷^,³⁹^,⁴⁵^,⁴⁶^,⁴⁸^,⁵¹^,⁵⁴ (Table 8).

Table 8.

Total WOMAC values before and after viscosupplementation.

Study/Interval	Baseline		Follow-Up		p-value
Study/Interval	Mean	SD	Mean	SD	p-value
1-month
Clementi et al. 2018¹⁹
UHMW	69.3	19.6	60.1	18.3	–
MMW	69.8	21	59.5	18.8	–
Spitzer et al. 2010⁵¹	64.27	1.27	–	–	<0.0001
Dıraçoğlu et al. 2009³⁹	17.26	2.49	12.27	2.40	<0.001
Tikiz et al. 2005³¹	63.9	21.3	37.1	28.4	<0.001
3-months
Clementi et al. 2018¹⁹
UHMW	69.3	19.6	56.8	14.5	–
MMW	69.8	21	57.1	17.4	–
Suppan et al. 2017⁵⁴	57.4	1.37*	79	1.13*	<0.001
Tikiz et al. 2005³¹	63.9	21.3	43.6	31.4	<0.001
Conrozier et al. 2003⁴⁶	157.2	53.5	104	79.7	<0.0001
6-months
Clementi et al. 2018¹⁹
UHMW	69.3	19.6	56.5	14.5	–
MMW	69.8	21	57.1	17.4	–
Tikiz et al. 2005³¹	63.9	21.3	38.7	30.3	<0.001
Pourbagher et al.⁴⁵	41.6	1.96	20	6.02	<0.05
26-weeks
Spitzer et al. 2010⁵¹	64.27	1.27	–	–	<0.0001
12-months
Clementi et al. 2018¹⁹
UHMW	69.3	19.6	57.2	13.7	–
MMW	69.8	21	57.1	16	–

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*Values reported as Standard Error of the Mean (SEM).

UHMW: Ultra High Molecular Weight; MMW: Medium Molecular Weight; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; SD: standard deviation.

Among the various included HA formulations and dosing schedules, no treatment protocol was found to be superior in terms of WOMAC total scores at respective follow-up (Table 3). Furthermore, there was mixed evidence regarding how HA injections performed on WOMAC function, WOMAC pain, and WOMAC total compared to other injection types (Table 4).

3.4. Harris Hip Score (HHS)

Six studies reported on Harris Hip Score (HHS) values following HA administration.²²^,³⁵^,³⁷^,³⁸^,⁴¹^,⁵⁵ A large majority of these studies found improvements in HHS following viscosupplementation, with 4 studies reporting statistically significant increases²²^,³⁵^,³⁷^,⁴¹ (Table 9). While Dallari et al. did not report specific HHS values at baseline and follow-up intervals, the authors did report significant improvements over time (p < 0.0005)³⁷. The only cohort to not achieve a significant improvement was the Synvisc cohort in the study by Van Den Bekerom et al.⁴¹

Table 9.

Harris hip scores (HHS) following hyaluronic acid injections.

Study/Interval	Baseline		Follow-Up		p-value
Study/Interval	Mean	SD	Mean	SD	p-value
1-month
Battaglia et al. 2013³⁸	62.9	–	78.02	–	–
6-weeks
Van Den Bekerom et al. 2008⁴¹
Adant	64.8	13.8	71.1	15.7	<0.001
Synocrom	66.8	13.8	77.4	14.7	<0.05
Synvisc	66.3	13.5	72.4	14.5	>0.05
3-months
Abate et al. 2017²²
HI LOW HA	66.7	16.5	72.3	12.1	0.001
HMW HA	65	14	69.5	12.5	0.0003
Battaglia et al. 2013³⁸	62.9	–	77.23	–	–
Gaston et al. 2007⁵⁵	52.9	12.5	63.6	26.3	–
6-months
Doria et al. 2017³⁵	62	9.8	74	12.3	0.0003
Abate et al. 2017²²
HI LOW HA	66.7	16.5	81.3	8.6	0.001
HMW HA	65	14	72.5	12.1	0.001
Battaglia et al. 2013³⁸	62.9	–	75.79	–	–
Gaston et al. 2007⁵⁵	52.9	12.5	73.3	18.6	–
12-months
Doria et al., 2017	62	9.8	75	11.4	0.0037
Battaglia et al. 2013³⁸	62.9	–	72.55	–	–

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HA: Hyaluronic Acid; HMW: High Molecular Weight; SD: standard deviation.

There was mixed evidence regarding the impact viscosupplementation formulations had on HHS values (Table 3). Additionally, in studies comparing HHS improvements between HA and PRP cohorts, there was no reported difference between these injection types (Table 4).

3.5. Patient global self-assessment

A total of 12 studies utilized patient global self-assessment scores to evaluate the efficacy of HA treatment.²¹^,26, 27, 28^,³⁰^,⁴⁰^,⁴²^,⁴⁶^,⁴⁹^,51, 52, 53 There was agreement across these analyses that values significantly increased following administration of HA. In addition to the data available in Table 10, Berg et al. found that 68% of patients considered that their hip OA had improved at 3-months, while only 1 patient (4%) felt that it had worsened (p < 0.001)⁵². Spitzer et al. similarly reported significant improvements between baseline values (66.66 ± 1.19) and scores recorded at 26-week follow-up (change: −16.67 ± 2.25; p < 0.0001).⁵¹ Additionally, Migliore et al. found significant improvements at all time intervals up to 12-months (all p-values <0.05) for their HA cohort.²⁸ In a later study, these authors further demonstrated significant improvements in patient self-assessment values up to 84-months (p < 0.05)²¹.

Table 10.

Patient global self-assessment scores among included studies.

Study/Interval	Baseline		Follow-Up		p-value
Study/Interval	Mean	SD	Mean	SD	p-value
1-month
Spitzer et al. 2010⁵¹	66.66	1.19	–	–	<0.0001
3-months
Eymard et al. 2017⁵³	7	–	5	–	<0.0001
Migliore et al. 2009²⁷	6.1	2.07	4.5	2.31	<0.001
Conronzier et al. 2006⁴²	66.1	12.4	41	28.5	–
Migliore et al. 2005³⁰	6	2	4	1.7	<0.05
Berg et al. 2004⁵²	–	–	19%	–	<0.0001
Conronzier et al. 2003⁴⁶	66.1	12.4	41	28.5	<0.0001
Mean 159 days
Conrozier et al. 2009²⁶	50.8	20.7	32.4	4.2	0.001
6-months
Migliore et al. 2009²⁷	6.1	2.07	4	2.06	<0.001
Migliore et al. 2005³⁰	6	2	4.5	1.9	<0.05
26-weeks
Brander et al. 2019⁴⁹	6.45	0.08*	–	–	<0.0001
Spitzer et al. 2010⁵¹	66.66	1.19			<0.0001
9-months
Migliore et al. 2005³⁰	6	2	4.4	2.9	<0.05
12-months
Migliore et al. 2005³⁰	6	2	3.5	2.6	<0.05

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*Values reported as Standard Error of the Mean (SEM). SD: standard deviation.

While there were no analyses that implemented this outcome measure to compare HA formulations, 4 studies compared HA to other intra-articular injection types. Most of these comparisons found no difference between management options, especially when evaluating longer term follow-up intervals (Table 4).

3.6. Rates of conversion to THA

Four analyses reported on rates of conversion to THA following viscosupplementation. Among this limited data, there was a large variation in reported conversion rates (range: 8%–55%). However, from 1 to 4 year follow-up, lower rates were reported compared to shorter term (6-weeks) and longer term (5-year) intervals (Table 11).

Table 11.

Reported rates of conversion to total hip arthroplasty.

Study/Interval	Rate
Study/Interval	Number	Percentage
6-weeks
Van Den Bekerom et al. 2006⁴³	33	55%
1-year
Migliore et al. 2012⁶²	18	8%
2-years
Migliore et al. 2012⁶¹	17	10%
Migliore et al. 2012⁶²	54	24.10%
3-years
Van Den Bekerom et al. 2008⁴¹	62	49%
4-years
Migliore et al. 2012⁶¹	32	18%
5-years
Migliore et al. 2012⁶²	155	69.20%

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4. Discussion

The implementation of HA has become increasingly used for the management of hip OA. Although multiple studies have shown its efficacy and anti-inflammatory effects, there is still a lack of consensus regarding whether HA administration should be common practice in the management of hip OA. Our analysis demonstrated that HA can effectively improve certain outcome measures and reduce pain among patients suffering from OA of the hip. However, there was mixed evidence regarding whether intra-articular HA was more beneficial compared to other infiltrations, such as PRP, corticosteroids, or placebo. Additionally, there was not enough evidence to suggest that outcomes differed when the molecular weight of the administered HA varied. Furthermore, HA administration was not conclusive for delaying the conversion to THA.

Although there was inconsistent evidence regarding whether HA outperforms other types of intra-articular injections, the relatively low rates of conversion to THA highlights the possible cost utility benefits associated with the use of HA. This was demonstrated in a recent study by Migliore et al. which found that HA use was economically beneficial when compared to managing hip OA with NSAIDs.⁵⁶ Similarly, Malik et al. found that HA injections only accounted for 0.4% ($19,384) of commercial costs during the 1-year prior to THA.⁵⁷ This value was substantially less than the 7.7% ($343,571) and 21% ($939,233) attributed to steroid injections and NSAIDs, respectively.⁵⁷ While these values may be affected by the relative implementation of each management strategy, the reduced costs associated with HA only further encourage its application in order to delay THA in this patient population.

The present analysis was unable to conclude that HA was superior to other conservative treatment options. Further data is needed before providers continue to implement viscosupplementation, despite its consistent ability to reduce the burden of hip OA. While a similar study has not been conducted for hip arthritis, a recent survey by Carlson et al. found that only 21% and 50% of responding orthopedic providers follow AAOS recommendations for stage 2 and 3 knee arthritis management, respectively.⁵⁸ Additionally, the authors reported that intra-articular HA was the most commonly implemented intervention for these stages of knee OA, despite similar AAOS guidelines recommending against its use.⁵⁹ Providers that continue to use viscosupplementation may consider the results of this systematic review. Recently, the European Viscosupplementation Consensus Group (EUROVISC) released a set of guidelines for optimizing the clinical results of HA.⁶⁰ Among other recommendations, the authors unanimously agreed that fluoroscopy or ultrasound should be implemented for safe administration into the hip joint.⁶⁰ Similarly, there was a strong recommendation that HA should be used among patients with mild to moderate OA that did not respond to NSAIDs or other non-pharmacological therapies.⁶⁰ While future analyses continue to be needed to ensure the safety and proper application of HA, these recommendations are a promising start.

Unfortunately, there was insufficient evidence available to identify which stages of hip OA would benefit the most from HA injections. Although Spitzer et al. and De Lucia et al. stratified their study population by Kellgren-Lawrence (KL) Grade, significant improvements at all time points were still demonstrated for individual cohorts.⁴⁸^,⁵¹ Similarly, OA severity did not appear to affect the results of comparisons to other intra-articular injection types.⁵¹ Additionally, while Battaglia et al. reported that degree of OA did not affect changes in HHS values, OA severity did influence changes in VAS.³⁸ Specifically, KL Grade IV patients had significantly lower score at 1-month follow-up. This significance was lost when looking at VAS scores 12-months after HA injection. Furthermore, both Suppan et al. (p = 0.195) and Eymard et al. (p = 0.18) reported that OA grade did not correlate with clinical response to treatment.⁵³^,⁵⁴ Given that significant improvements in pain and function were demonstrated in a large majority of included studies and that these studies primarily evaluated patients with KL Grades II-III, these findings may support the EUROVISC recommendation that patients with mild to moderate OA should be considered as reasonable candidates for treatment. However, since patients with KL Grade IV OA were additionally found to benefit from HA injections, additional studies are still needed in order to determine when HA should be indicated in this population more readily considered for THA.

Our systematic review has several limitations. One of the most significant limitations pertains to conflicts of interests among study authors as well as how funding sources may have influenced study design and analysis. Certain studies indicating positive results following HA administration were conducted by authors with conflicts related to the manufacturers of the implemented viscosupplementation.²¹^,⁴⁰^,⁵¹^,⁵³^,⁶¹^,⁶² Similarly, 9 studies were funded by pharmaceutical companies.²³^,²⁷^,²⁸^,⁴²^,⁴⁹^,⁵¹^,⁵⁴^,⁶¹^,⁶² Unfortunately, since a large proportion of studies (n = 18) failed to disclose any conflicts of interest or funding information, it is unclear to what extent industry or financial relationships may have influenced the results of the included analyses. Among studies there was a paucity of randomized controlled trials (RCTs) evaluating the efficacy of HA to other types of intra-articular injections. Similarly, certain included RCTs suffered from relatively small sample sizes and short follow-up periods.²⁷^,³⁷^,³⁸^,⁵⁰ Additionally, there was considerable variation across studies regarding HA formulations, dosing schedules, and post-injection protocols. Due to this lack of uniformity, we felt that a combined analysis would be inappropriate since factors such as molecular weight and frequency of infiltration could substantially influence results. Similarly, we were unable to control for the severity of arthritis in each treatment cohort. Although a majority of studies reported on KL Grades II and III, it is unclear if there was consistent classification among researchers or whether the findings of this analysis could extend to patients with more severe hip arthritis. Furthermore, we did not report on other outcome measures, such as the incidence of adverse events (AEs), nonsteroidal anti-inflammatory drug (NSAID) use, or radiographic measurements. Despite these limitations, we reported on outcomes following HA administration in the most comprehensive systematic review to date.

As hip osteoarthritis continues to be a challenging and financially burdensome disorder to manage, providers continue to seek efficacious and safe treatment options to restore function and reduce pain. Although the use of HA is not currently recommended by the AAOS (nor approved for use in the hip by the Food and Drug Administration), non-comparative studies demonstrated that HA may produce select functional and outcome benefits. However, there was not enough evidence in the current literature regarding whether HA is superior to placebo or other types of intra-articular injections. Future studies should continue to compare HA to other treatment modalities in RCTs with larger sample sizes. Similarly, researchers should aim to implement consistent treatment protocols in order to reduce potential confounding effects.

Funding

No funding or financial support was received for this review.

Declaration of competing interest

A.F.K. reports the following disclosures: research support (Zimmer Biomet, DePuy Synthes), paid presenter or speaker (Corin, DePuy Synthes, Heraeus Medical, and Zimmer Biomet), paid consultant (Pacira Pharmaceuticals, Heraeus Medical, DePuy Synthes, and Zimmer Biomet), stock or stock options (Zimmer Biomet, Johnson & Johnson, and Procter & Gamble), IP royalties (Innomed), board or committee member (AAOS and AAHKS), and editorial or governing board (BMC Musculoskeletal Disorders). A.J.A., L.T.S., A.K.E., and S.H.J. have nothing to disclose.

Footnotes

^☆

This review did not require the approval of the Cleveland Clinic Foundation Institutional Review Board.

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PERMALINK

Viscosupplementation for hip osteoarthritis: Does systematic review of patient-reported outcome measures support use?☆

Alexander J Acuña

Linsen T Samuel

Stacy H Jeong

Ahmed K Emara

Atul F Kamath

Abstract

Introduction

Methods

Results

Discussion

1. Introduction

2. Methods

2.1. Literature search

2.2. Study selection

Fig. 1.

Table 1.

3. Results

3.1. Lequesne Index

Table 2.

Table 3.

Table 4.

3.2. Visual analog scale

Table 5.

3.3. WOMAC

Table 6.

Table 7.

Table 8.

3.4. Harris Hip Score (HHS)

Table 9.

3.5. Patient global self-assessment

Table 10.

3.6. Rates of conversion to THA

Table 11.

4. Discussion

Funding

Declaration of competing interest

Footnotes

References

ACTIONS

PERMALINK

RESOURCES

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Viscosupplementation for hip osteoarthritis: Does systematic review of patient-reported outcome measures support use?^☆