Exploratory study of the efficacy and safety of treatment with high-low molecular weight hybrid hyaluronic acid in patients with plantar fasciitis: One-year follow-up

Abstract

Introduction

Plantar fasciitis (PF) is a common musculoskeletal injury that can occur in adults of all ages and activity levels. This condition accounts for more than 1 million medical visits annually in the United States alone. Despite its name, PF is considered a degenerative condition rather than a primary inflammatory disorder. It is characterised by pain in the medial part of the heel that worsens with weight-bearing activity and prolonged standing. Treatment for PF can be conservative, including stretching complemented by formal physical therapy, NSAIDs, and orthotics. If symptoms have not improved after these options, the use of injectable treatments should be considered. If symptoms persist for more than 6 months, surgical release could be considered as a last resort. Different studies have demonstrated the efficacy and safety of high molecular weight hyaluronic acid (HA) injections in the treatment of patients with PF.

Objectives

The objective of the study was to evaluate the efficacy and safety of treatment with hybrid high-low molecular weight hyaluronic acid (HA) in patients diagnosed with plantar fasciitis through retrospective analysis of medical records.

Materials and methods

Patient functionality was assessed using the Spanish-validated Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ), and pain level was measured with the Verbal Numeric Rating Scale (VNRS), both before the procedure and after 12 months of post-treatment follow-up, in 10 patients diagnosed with PF who were administered hybrid high-low molecular weight HA (Sinovial HL® 1 ml) through ultrasound-guided injection into the plantar fascia. In all cases, the thickness of the plantar fascia was evaluated by ultrasound before the procedure and at 12 months.

Results

A significant reduction in pain assessed by the VNRS was observed when comparing baseline data to values at 12 months post-procedure (p < .001). In all cases, patients reported total absence of pain 12 months after the HA injection. Likewise, a statistically significant reduction in MOXFQ scores was observed between baseline values and those obtained at the 12-month follow-up. The mean scores decreased from 57.2 ± 4.3 points at baseline to 2.5 ± 2.8 points at 12 months, with a median difference of −55 points (IQR: −58.2 to −50.8; p = .002). Regarding the evaluation of ultrasound changes in plantar fascia thickness, the analysis revealed a statistically significant reduction at 12 months after the procedure compared to baseline measurements (median difference: −2.25 mm, IQR: −2.85 to −1.95; p = .002). The body mass index (BMI) was 27.8%, and the predominant gender was male (70%) compared to female (30%). The baseline characteristics of the patients and the results of the tests performed are shown in Table 1.

Conclusions

Ultrasound-guided infiltration with hyaluronic acid hybrid high-low molecular weight into the plantar fascia in patients with plantar fasciitis or intrafascial fibre rupture is an effective and safe treatment that maintains its positive effects for at least one year after the procedure. The use of ultrasound plays a fundamental role both at the time of infiltration and in the follow-up of the condition.

Resumen

Introducción

La fascitis plantar (FP) es una lesión musculoesquelética común que puede presentarse en los adultos de todas las edades y niveles de actividad. Esta afección representa más de 1 millón de visitas médicas anuales tan solo en los EE. UU. A pesar de su nombre, la FP se considera una afección degenerativa más que una afección inflamatoria primaria. Se trata de una afección caracterizada por dolor en la parte medial del talón que se exacerba con la actividad de carga de peso y bipedestación prolongada. El tratamiento de la FP puede ser conservador, con estiramientos complementados con fisioterapia formal, AINE y ortesis. Si los síntomas no han mejorado después de estas opciones debe considerarse el uso de tratamientos inyectables. En caso de que los síntomas continúen persistiendo durante más de 6 meses, se podría considerar la liberación quirúrgica como último recurso. Diferentes estudios han demostrado la eficacia y seguridad de las inyecciones de ácido hialurónico (AH) de alto peso molecular en el tratamiento de los pacientes con FP. Con resultados a largo plazo, sin las complicaciones del uso de corticoides.

Objetivos

El objetivo del estudio fue evaluar la eficacia y seguridad del tratamiento con AH híbrido de alto 7 bajo peso molecular en los pacientes diagnosticados de FP mediante el análisis retrospectivo de historias clínicas.

Materiales y métodos

Se determinó tanto la funcionalidad de los pacientes mediante el cuestionario pie/tobillo de Manchester-Oxford (MOXFQ) validado en español como el grado de dolor, medido con la escala numérica verbal (ENV), antes del procedimiento y tras 12 meses de seguimiento postratamiento, en 10 pacientes diagnosticados de FP, a los cuales se administró AH híbrido de alto/bajo peso molecular (Sinovial HL® 1 ml) mediante infiltración ecoguiada de la fascia plantar. En todos los casos se evaluó el grosor de la fascia plantar mediante ecografía antes del procedimiento y a los 12 meses.

Resultados

Se observó una reducción significativa del dolor evaluado mediante la ENV al comparar los datos basales y los valores a los 12 meses del procedimiento (p < 0,001). En todos los casos, los pacientes referían una ausencia total del dolor a los 12 meses de la infiltración de AH. Del mismo modo, se pudo observar una reducción estadísticamente significativa en las puntuaciones del MOXFQ entre los valores basales y los valores obtenidos a los 12 meses de seguimiento. Las puntuaciones medias disminuyeron desde 57,2 ± 4,3 puntos en el momento basal hasta 2,5 ± 2,8 puntos a los 12 meses, con una diferencia mediana de −55 puntos (RIC: −58,2 a −50,8; p = 0,002). Respecto a la evaluación de los cambios ecográficos en el grosor de la fascia plantar, el análisis reveló una reducción estadísticamente significativa a los 12 meses tras el procedimiento en comparación con las mediciones basales (diferencia mediana: −2,25 mm; RIC: −2,85 a −1,95; p = 0,002). El indice de masa corporal (IMC) fue del 27,8% y el género predominante el masculino con el 70% en comparación con el 30% del género femenino.

Conclusiones

La infiltración con AH híbrido de alto/bajo peso molecular de la fascia plantar en los pacientes con FP o rotura fibrilar intrafascial es un tratamiento eficaz y seguro que mantiene sus efectos positivos como mínimo un año tras el procedimiento. El uso de la ecografía tiene un papel fundamental tanto en el momento de la infiltración como en el seguimiento de la afección.

Introduction

Plantar fasciitis (PF) is a common musculoskeletal condition affecting the foot. It can occur in adults of all ages and activity levels. It is estimated that approximately 10% of people will experience this condition at some point in their lives.¹ Specifically, PF accounts for over 1 million doctor visits in the US alone each year.² Despite its name, PF is considered a degenerative condition rather than primarily inflammatory.³

Around 12% of patients with PF experience a rupture or tear of the plantar fascia, which can be complete or partial.⁴ In most cases, there is a history of treatment with local steroid injections.⁴ Furthermore, a high rate of complications has been observed, such as plantar fat necrosis, also known as fat pad syndrome, which occurs in 10% of cases. Other complications include alterations in the pull-up mechanism, inferior calcaneal nerve dysfunction, toe deformities (claw or hammer toes), and distal plantar fascia tears. It is known that all of these sequelae are permanent and that most are difficult to treat.¹⁷

Plantar fasciitis is characterised by pain on the medial side of the heel that worsens with weight-bearing activity, as well as after periods of rest or non-weight-bearing.² The condition is usually chronic, and the typical symptoms such as pain, swelling, redness, and stiffness can last for more than a year.²

PF is common but treatable.⁵ Initially, treatment for plantar fasciitis may be conservative, involving stretching supplemented by formal physical therapy, if necessary. Other first-line non-invasive treatments include NSAIDs and orthotics. A night splint may be added, although compliance is poor and the cost is relatively high. If symptoms have not improved after trying these options, injectable treatments should be considered.⁵ If patients’ symptoms persist for more than 6 months, shockwave or radiofrequency therapy may be considered. Surgical release is usually a last resort.⁵ Meanwhile, for acute PF tears, there are currently no consistent therapeutic strategies, and treatments in the various existing case series differ considerably.⁶ The role of platelet-rich plasma (PRP) therapy or shockwave therapy in these patients is unclear.^6,7 Furthermore, given the small number of reported cases, the indications and outcomes of surgical treatment remain unknown.⁸

The efficacy and safety of the cooperative hybrid complex based on high- and low-molecular-weight hyaluronic acid (HA) have been demonstrated in the treatment of osteoarthritis.⁹ Furthermore, the efficacy of high-molecular-weight HA injections in treating patients with PF has been demonstrated in some studies.^10,11 However, there are currently no published studies or clinical case reports describing the use of HA in treating PF rupture.¹¹

Ultrasound monitoring has also been proposed as an excellent method for evaluating the efficacy of various therapies.¹²

Materials and methods

This study evaluated the efficacy and safety of hybrid high-low molecular weight HA (Sinovial® HL 1 ml) in ten consecutive patients with PF or an intrafascial fibrillar tear of the PF, who were treated between April and June 2023. The patients were not professional athletes and had no history of prior treatment with steroids or injected platelet-derived growth factors.

None of the patients had undergone shockwave or radiofrequency therapy within 3 months before or after treatment.

Hybrid high-low molecular weight hyaluronic acid was administered via ultrasound-guided infiltration of the plantar fascia in the longitudinal plane of the medial aspect of the foot (with the ultrasound probe placed 2–3 cm below the medial malleolus in the calcaneal region). The area of maximum convexity of the medial cord of the plantar fascia in the hindfoot was located using double verification in the axial plane and the posteroinferior tuberosity of the calcaneus as a landmark (anatomical reference point). After aseptic and antiseptic preparation, with the ultrasound probe protected by a sterile sheath, 1–2 ml of perifascial anaesthetic was administered, and ultrasound-guided injection is performed without removing the guide needle. One millilitre of the local anaesthetic was injected into the surface of the plantar fascia. In a second step, an anaesthetic block of the inferior calcaneal (Baxter's) nerve was performed when involvement of this nerve branch was confirmed. In our series, only one patient presented with clinical signs of abductor digiti minimi pedis paralysis due to Baxter's nerve involvement, with moderate fatty atrophy of the abductor digiti minimi pedis visible on magnetic resonance imaging (Fig. 1).

Fig. 1.

HA injection technique for the plantar fascia. 1: Plantar fat pad; 2: Abductor hallucis muscle; 3: Calcaneus; 4: Abductor digiti minimi pedis; A: Medial band of the plantar fascia; B: Lateral band of the plantar fascia.

In all cases, the patient's functional status was assessed using the Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ), validated in Spanish,¹³ and the degree of pain was measured using the verbal numerical rating scale (VNRS), both before the procedure and after 12 months of post-treatment follow-up. Similarly, plantar fascia thickness was assessed by ultrasound before the procedure and at 12 months. For statistical analysis, the Wilcoxon test for paired samples was used (results are shown as mean and interquartile range [IQR]); in addition, body mass index (BMI) was calculated, and gender was considered. No patient required shockwave therapy, radiofrequency treatment or physiotherapy following the procedure. Orthopaedic insoles were prescribed for all patients once the pain had subsided.

Results

The study included a cohort of ten patients (mean age: 59.5 years ± 11.17) with PF rupture or intrafascial fibre rupture of the PF. The mean BMI was 27.8, and 70% of the cohort was male, compared to 30% female. The baseline characteristics of the patients and the results of the tests carried out are shown in Table 1.

Table 1.

Characteristics of the patients included in the analysis and scores on the Verbal Numerical Rating Scale (VRNS), the Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ), and plantar fascia thickness measured by ultrasound; before the procedure and 12 months afterwards.

Patient	Age (in years)	Sex	BMI	Type of injury	Type of foot	Baseline VRNS	VRNS at 12 months	Baseline MOXFQ	MOXFQ at 12 months	Baseline fascia thickness (mm)	Fascia thickness (mm) at 12 months
1	68	M	28.1	IFR	Cavovalgus	9	0	55	1	4.0	3.6
2	53	M	25.5	PF	Planus	8	0	64	3	5.9	5.6
3	53	F	22	IFR	Planus	8	0	60	2	6.9	3.8
4	81	M	27.6	IFR	Planus	7	0	52	1	5.1	2.9
5	64	F	28.1	IFR	Planus	8	0	58	2	7	3.4
6	42	M	32.7	PF	Planus	7	0	52	2	6.8	4.1
7	69	M	29.4	IFR	Planus	7	0	57	10	5.8	3.8
8	60	M	28.7	IFR	Cavus	9	0	62	3	6.4	4
9	45	M	26.8	PF	Cavus	7	0	56	1	7.3	4.9
10	60	M	29.1	PF	Planus	9	0	56	1	5.2	3.4

BMI: body mass index; F: female; IFR: intrafascial rupture; M: male; PF: plantar fasciitis.

Significant reductions in pain, as assessed by the VNRS, were observed when comparing baseline data with values 12 months after the procedure (p < .001). In all cases, patients reported an absence of pain 12 months after the HA injection. Similarly, a statistically significant reduction in MOXFQ scores was observed between baseline values and those obtained at the 12-month follow-up. Mean scores decreased from 57.2 ± 4.3 points at baseline to 2.5 ± 2.8 points at 12 months, with a median difference of −55 points (IQR −58.2 to −50.8; p = .002). Regarding the assessment of changes in plantar fascia thickness, the analysis revealed a statistically significant reduction at 12 months post-procedure compared to baseline measurements (median difference: −2.25 mm; IQR: −2.85 to −1.95; p = .002).

These positive results were observed across the three variables analysed, from the very first weeks following treatment (Fig. 2).

Fig. 2.

One-year progression of the analysed variables (VNRS, MOXFQ, and plantar fascia thickness measured by ultrasound).

None of the patients experienced any significant adverse effects.

Discussion

While there are many therapeutic options available for PF, there is currently no established standard treatment.¹⁰ In recent years, results have been reported for treatment with PRP and extracorporeal shockwave therapy. However, these treatments remain controversial.¹⁰ When conservative treatment fails to relieve pain, surgery may be considered. However, surgery may be accompanied by persistent pain (in up to a quarter of surgically treated patients); furthermore, there are potential risks of complications (including nerve injury during endoscopic release).¹⁰ A systematic review by Monteagudo et al. revealed that PRP is more effective than corticosteroids in terms of pain relief and functional improvement.¹⁷ The 2017 consensus statement from the American Orthopaedic Foot and Ankle Society concluded that corticosteroids do not alter the course of the disease and that their beneficial effect beyond four weeks is limited.¹⁷ Furthermore, they are associated with a high rate of plantar fascia rupture.¹⁸

Therefore, given its proven efficacy, safety and ease of use in routine clinical practice, HA injection should be considered a potential treatment of choice for patients with PF.

Some studies have shown that the injection of high-molecular-weight HA is an effective treatment for PF.^10,11 Furthermore, the use of HA has recently extended to other extra-articular areas, such as Achilles tendinopathy and ligament injuries, thanks to its anti-inflammatory properties and ability to restore viscoelasticity.¹⁴ While the mechanism by which HA acts on enthesopathies remains unclear, its ability to relieve pain, inhibit cartilage degeneration, prevent tissue adhesion, and hinder microangiogenesis and neurogenesis has been confirmed.¹⁰ It is worth noting that, if performed correctly and under aseptic conditions, HA injection is a safe technique.¹⁵

Kumai et al. published a prospective, double-blind, randomised controlled trial involving 168 patients randomised into three treatment arms: injections of 25 mg of high-molecular-weight animal-derived HA (2.5 ml at 1%) (2700 kDa); injections of 8 mg of HA (.8 ml at 1%) of low molecular weight; or injections of .25 mg of HA (2.5 ml at .01%; control group (Suvenyl®; Chugai Pharmaceutical Co., Ltd., Tokyo, Japan). This study concluded that the injection of high-molecular-weight HA is an effective treatment for PF, significantly reducing pain after 5 weeks of follow-up, with no serious adverse reactions related to the product observed.¹⁰ Meanwhile, Raeissadat et al. published a randomised, triple-blind clinical trial involving 75 patients with symptoms of PF lasting at least 3 months. The patients were randomised into two treatment groups: one group received a single injection of HA (1 ml of HA 20 mg) with a high molecular weight (>2000 kDa) + 1 ml of 2% lidocaine, while the other group was treated with a corticosteroid injection (1 ml of methylprednisolone 40 mg) + 1 ml of 2% lidocaine. The study results showed that both corticosteroids and HA were effective treatments for improving pain and function in patients with plantar fasciitis after a 24-week follow-up (with neither treatment demonstrating superiority), although corticosteroids showed a tendency towards more rapid improvement in the short term (week 8).¹¹ Furthermore, this study demonstrated a significant reduction in plantar fascia thickness, assessed at 8 and 24 weeks following the injection, in both the group of patients treated with HA and the group that received corticosteroid injections as treatment.¹¹

The significance of the case series analysed in this paper lies in two key aspects. Firstly, it presents the use of state-of-the-art HA (hybrid high-low molecular weight HA) as an effective and safe therapeutic option. Secondly, it demonstrates that imaging techniques (ultrasound) can be used to objectively confirm a clear reduction in lesions associated with the condition.

Treatment with state-of-the-art HA injections (hybrid high-low molecular weight HA) offers a highly significant clinical improvement from the very first days of treatment without any notable adverse effects. Clinical improvement has been demonstrated through both MOXFQ assessment (improvement resulting in a recovery of functionality enabling all patients to lead a normal life) and through pain assessment using a VAS. The VAS showed that pain disappeared in all cases following the injection of hybrid HA, a remission that was maintained throughout the 12-month follow-up period.

A hybrid HA molecule with both high and low molecular weights is now available, which could be the key to treating PF, offering all the benefits of low-molecular-weight HA used in tendon conditions, as well as the mechanical benefits of high-molecular-weight HA demonstrated in joint conditions.¹⁶

While hyaluronic acid (HA) generally does not have a rapid analgesic effect, and its full benefits may not be evident until at least 4 weeks after the first injection, a single administration of a high/low molecular weight hybrid HA has been shown to provide rapid symptomatic relief. There were statistically significant differences in pain intensity between groups in favour of the hybrid HA in patients with osteoarthritis.⁹ The results observed in the patient series presented in this paper support the aforementioned data on the treatment of PF patients.

Finally, this publication highlights the value of ultrasound in treating and monitoring plantar fasciitis. Musculoskeletal ultrasound is relatively quick, cost-effective, and is widely available. It enables the detection of thickening, tears, and compromise of the plantar fat pad, as well as other signs.¹¹ While an ultrasound scan is not required for a diagnosis of plantar fasciitis, it is highly valuable in assessing the efficacy of potential treatments,^11,12 including HA¹¹ (Fig. 3). Furthermore, an ultrasound-guided injection is very useful in overcoming the technical challenge of accurately delivering HA into the plantar region, thereby minimising the likelihood of an unsatisfactory response to treatment.¹⁰

Fig. 3.

Example of changes in the plantar fascia (patient number 3) before the injection and 12 months later (ultrasound images [A and B] and nuclear magnetic resonance images [C and D]).

In conclusion, the injection of the cooperative hybrid complex based on high- and low-molecular-weight HA into the plantar fascia in patients with plantar fasciitis or intrafascial fibre tears is an effective and safe treatment, with beneficial effects lasting at least one year following the procedure. The treatment may therefore offer an alternative to avoid the dreaded complications associated with corticoid steroid use, which in most cases cause irreversible sequelae in patients.¹⁸ The use of ultrasound plays a fundamental role at the time of injection and in follow-up of the condition.

Limitations of the study

Despite the excellent results demonstrated in this study, which aimed to highlight a safe and effective alternative for treating FP, it is important to note that this is a retrospective analysis of results obtained from a small group of patients. Therefore, a prospective randomised study would be required to confirm these results. The retrospective nature of this study also limited the analysis of interim results between baseline data and data at 12 months, as these were not systematically recorded (data from the first few weeks, and at 3 and 6 months following the injection, are available for only some of the patients). Furthermore, a new double-blind study in a population with a high prevalence of the condition, such as athletes aged between 18 and 48 years, could be very useful to compare the outcomes of using hybrid hyaluronic acid (HA) versus platelet-rich plasma (PRP). This would provide a new treatment option and, in future, avoid the use of corticosteroids in plantar fasciitis due to their numerous documented complications and short-lived response.^17,18

Level of evidence

Level of evidence iv.

Ethical considerations

We declare that this research study complies with all the necessary ethical considerations and requirements for publication and was carried out with the approval of the Ethics Committee of the Quironsalud-Catalonia Hospital Group, under approval number: 2025/93-TRAU-HQB.

Funding

We declare that this study was conducted using the researchers’ own funds and that no external funding was received. We are also grateful for the voluntary collaboration of the statistical adviser and all the professionals who assisted us in achieving our objectives.

Conflict of interests

The authors have no conflict of interests to declare

Acknowledgements

We would like to thank Sergi Ampurdanés for his support in editing this article.