EFFECTIVENESS OF DEXTROSE PROLOTHERAPY IN CHRONIC PLANTAR FASCIITIS: A CROSS-SECTIONAL STUDY

. Prolotherapy is a very cost-eﬀecve, and OPD-based procedure that has shown promising results in many tendinopathies. There are no other risks involved in this procedure, and pa�ents can start light ac�vi�es immediately a�er the injec�on


INTRODUCTION
Plantar fascia (PF) is an aponeurosis (thick connec ve ssue) extending from the calcaneal tuberosity to the heads of the metatarsals that support the arch of the foot. Due to the repe ve micro-trauma, there is tendinopathy over the calcaneal tuberosity, leading to heel pain, also known as Plantar Fascii s (PF). The pain is usually worse while ge ng out of bed in the morning, fades gradually with ac vi es, and starts up again on prolonged standing, thereby limi ng 1 the ac vi es. In a recent systema c review and metaanalysis, excessive dorsiflexion, a high body mass index (BMI), and a high body mass were considered the most 2 important risk factors for plantar fascii s. Plantar fascii s is usually diagnosed on a pa ent's history and clinical examina ons. Other diagnos c modali es, such as X-rays, ultrasound (US), and Magne c Resonance Imaging (MRI) do help in atypical cases. A calcaneal spur can be seen on x-rays, and thickening of plantar fascia >4mm is usually sugges ve of PF. US is also helpful in monitoring disease ac vity during [3][4][5][6] the rehabilita on period.
PF is usually managed conserva vely by most clinicians. Conserva ve methods include stretching exercises, nonsteroidal an -inflammatory drugs, arch support, night splints, physical therapy, extracorporeal shockwave therapy 7,8 (ESWT), and injec ons. Injec ons include cor costeroids, platelet-rich plasma (PRP) therapy, administra on of 9 botulinum toxin, acupuncture, dry needling, and prolotherapy. Although cor costeroids have shown short-term effec veness in relieving the pain of PF, the long-term effect is s ll not 10 clear.
Prolotherapy (PrT) is an injec on-based technique in which a small amount of irritant solu on is injected at the degenerated site. Animal model studies suggest there is local inflamma on at the injec on site, which s mulates growth factors, thereby s mula ng fibroblasts and repairing the degenera ve musculoskeletal condi ons. Hyperosmolar dextrose solu on is commonly used, usually three mes in short intervals, to s mulate healing. Prolotherapy is also associated with minimal to no complica on risks and a high 11 success rate with a short period of rehabilita on.
Despite the good results of prolotherapy, only a few studies 12 have been done to support its efficiency. Hence, this study is done to establish the efficacy of dextrose prolotherapy using clinical, func onal, and sonographic tools, so that this cost-effec ve, no-risk procedure can be brought into prac ce in pa ents who have failed other conserva ve measures.

METHODOLOGY
This prospec ve, cross-sec onal study, was conducted from July 2021 to December 2021 at Birat Medical College Teaching Hospital a er taking permission from the Ins tu onal Review Commi ee (IRC). Pa ent selec on was done using inclusion and exclusion criteria. Inclusion criteria included (i) 18 years of age or older (ii) having unilateral resistant heel pain for at least six months (iii) having undergone non-steroidal an -inflammatory therapy for at least one month, exercise therapy, and arch support among other conserva ve treatments but with no desired outcome (iv) morning pain measured by the visual analog scale (VAS) being above 5 (v) plantar fascia thickness measured by ultrasonography being >4 mm, and (vi) providing informed consent. Exclusion criteria included (i) bilateral PF (ii) presence of other diseases of the foot or ankle (arthri s, old or new fractures, tarsal tunnel syndrome, etc.) (iii) history of surgical treatment for PF (iv) having received steroid injec ons for PF within the last six months (v) having undergone oral non-steroidal an -inflammatory therapy in the last week (vi) presence of chronic pain syndromes (vii) being diagnosed with diabetes mellitus, rheumatologic disease, central neurologic diseases (epilepsy, cerebro vascular disease, etc.) or mental disorders causing lack of insight and judgment (schizophrenia spectrum and other psycho c disorders, bipolar and related disorders, etc.) (viii) the presence of peripheral vascular disease or peripheral neuropathy related to the lower extremi es (ix) having a disorder or using medica on that impairs the bleeding profile (x) Presence of infec on at the injec on site. A total of 66 pa ents were included in the study, who received two prolotherapy injec ons in a gap of two weeks and were followed up a er 12 weeks. The objec ve of the study was to evaluate the efficacy of prolotherapy injec ons in pa ents with chronic plantar fascii s.

Ultrasound Examina on
All the ultrasound (USG) examina ons were done by a single radiologist using the Voluson S10 Expert (GE Healthcare) with a frequency of 5-17 MH. The first USG was done before prolotherapy, the thickness of the PF was noted, and pa ents with PF thickness >4 mm were included in the study (Fig 1). The second USG was done at 12 weeks following the second injec on, and PF thickness was noted again.

Hyperosmolar Dextrose Injec on
Using a 27 gauge needle, 1 ml of 50% dextrose solu on (25gm/50ml) mixed with 1 ml of 2% lidocaine; making the strength of dextrose 25%, was injected by palpa on technique at plantar fascia a achment sites by a single health professional expert in musculoskeletal prolotherapy.
The procedure was done following all asep c guidelines. Following prolotherapy, no NSAIDs were given for 72 hours to avoid interac on with the ac on of dextrose prolotherapy. The pa ents were asked to follow up a er two weeks for the second prolotherapy injec on. They were asked to avoid heavy ac vity for at least 12 weeks.

Data Collec on and Analysis
A er informed wri en consent, clinical details and findings were noted as per the proforma and ques onnaires. Visual Analogue Scale at Rest (VAS-R), Visual Analogue Scale at Ac vity (VAS-A), Foot Func on Index (FFI), and PF thickness were noted before prolotherapy and 12 weeks a er the second injec on. The data were collected and analyzed using IBM SPSS version 23. MS Excel was used for data entry. A P-value of <0.05 was considered significant.

RESULTS
There were 66 adult pa ents included in the study, out of which 39 pa ents (59.1%) were female and 27 pa ents (40.1%) were male. Their age ranged from 26 to 68 years, with a mean age of 43.91 and a standard devia on (SD) of 10.225. The mean BMI was 25.758 with an SD 2.69 (range: 19.6-33.2). There were significant improvements (p<0.05) noted in VAS-R, VAS-A, FFI, and ultrasonographic findings (PF thickness). The clinical score (VAS-R and VAS-A), func onal score (FFI), and ultrasonographic findings (PF thickness) details are depicted in the below-men oned table 1.

DISCUSSIONS
Plantar fascii s is a chronic overuse injury leading to degenera ve changes, that is, the breakdown of type I collagen and proteoglycans. This ul mately reduces the 13,14 strength of the fascia and predisposes it to reinjury. The present study shows significant improvement in VAS-R, VAS-A, FFI, and plantar fascia thickness in pa ents who have received prolotherapy. Prolotherapy is believed to be an effec ve therapeu c measure in cases of chronic tendini s such as lateral epicondyli s, and plantar fascii s. The mechanism works on the principle which helps in the adequate forma on of 15,16 fibroblasts and connec ve ssue. Prolotherapy is the local infiltra on of a hypertonic dextrose solu on or an irritant solu on. One of the mechanisms suggests the ini a on of an inflammatory cascade, ul mately leading to the sclerosis of the pathological tendons, fascia, etc. However, another theory suggests that the s mula on of 17,18 growth factors ul mately helps in so ssue healing. Regenera ve injec on therapy, also known as prolotherapy, has shown effec veness in trea ng painful ligament and tendon pathologies. The study also suggests the forma on of collagen and fibroblast prolifera on, which are associated with the strengthening of tendons and ligaments, improved 19,20 joint func on, and pain reduc on. Nowadays, mul ple injec on-based procedures are in prac ce for chronic plantar fascii s. The commonly prac ced procedure is a local steroid injec on, which has shown promising results in decreasing inflamma on, and, ul mately, pain reduc on. Although the use of local steroids has shown good short-term benefits, there are several side effects associated with its use such as localized infec on, calcaneal osteomyeli s, lateral plantar nerve injury, plantar 21,22 fascia rupture, and plantar fat pad atrophy. Platelet-rich plasma (PRP) is another injec on-based procedure that has shown good results in plantar fascii s. PRP has shown good ssue healing, pain relief, and func onal as well as clinical outcomes. However, PRP is an invasive procedure and also lacks a standardized prepara on protocol. Prolotherapy, when compared to steroid injec ons and PRP, is simple to prepare, easy to use, non-invasive, less costly, and provides 21,23 be er and longer dura on of ssue healing. In a systemic review and meta-analysis on the effec veness of dextrose prolotherapy in plantar fascii s done by Wei-Fu Lai et al, six studies with 388 pa ents diagnosed with plantar fascii s were included in the meta-analysis. The study revealed be er pain scores improvement and func onal outcomes in the long term for pa ents treated with dextrose prolotherapy compared to those treated with the cor costeroid injec ons, and the physiotherapy group. However, no significant differences were found between pa ents treated with dextrose prolotherapy and plateletrich plasma. The meta-analysis concluded dextrose prolotherapy as a safe and effec ve treatment op on, and also emphasized further studies with a standardized 24 protocol. In a study conducted by Ersen et al, a randomized-controlled trial was done on 26 pa ents receiving prolotherapy and 24 pa ents in control groups. The study concluded significant improvements in VAS, FAOS (Foot and Ankle Orthopedic Society), and FFI scores at 42 and 90 days of follow-up, which 25 is consistent with the present study. In a pilot study conducted by Maxwell et al, sonographically guided intratendinous injec ons of hyperosmolar dextrose were given to pa ents with Achilles tendinosis. The study yielded a significant decrease in VAS pain scores at rest and 26 during loading ac vi es. Ryan et al conducted a pilot study in which they gave ultrasound-guided dextrose/lidocaine injec ons to 20 pa ents with chronic plantar fascii s. The result showed significant improvement in pre-test and post- 27 test VAS values, which is in correla on with our study. Yelland et al conducted a randomized trial for painful Achilles tendinosis. They formed 3 random groups: the first group received prolotherapy, the second group with eccentric loading exercises, and the third group received both treatments. They showed be er results with groups . 20 receiving both treatments than with the other two groups Scarpone et al conducted a pilot study in which prolotherapy was used for trea ng lateral epicondyli s. The study showed improved long-term effects of prolotherapy in pa ents with 28 refractory lateral epicondyli s. Yildiz et al in their study followed the protocol of three injec ons of Prolotherapy three weeks apart in recrea onal athletes suffering from patellofemoral pain syndrome and achieved significant 29 clinical improvement. In a study conducted by Ang et al, steroid injec ons were given using an ultrasonography-guided technique and a palpa on technique. Both techniques showed no significant th difference between the groups at the end of the 25 month sugges ng that palpa on technique is equally effec ve 30 compared to ultrasonographic-guided injec on. Similarly, in a study conducted by Yucel et al, a comparison was done that included three techniques for steroid injec ons. The techniques were ultrasound-guided, palpa on-guided, and scin graphy-guided steroid injec ons. The study concluded that steroid injec ons can be given either by the ultrasoundguided technique or by the palpa on method without any 31 significant difference. Both the studies, Ang et al and Yucel et al, support our palpa on technique method used for prolotherapy. AH Apaydin et al in their study followed the protocol of two injec ons of prolotherapy in recrea onal athletes with plantar fascii s, given two weeks apart, and showed significant improvement in VAS and Foot and Ankle 32 outcome scores. In our study as well, we gave two prolotherapy injec ons two weeks apart and yielded similar results.

CONCLUSION
There are mul ple treatment modali es for chronic plantar fascii s, which include both conserva ve and surgical management. However, dextrose prolotherapy can be considered a safe, economical, and effec ve treatment module for plantar fascii s that has shown significant improvement in pain, func onal outcomes, and pa ent sa sfac on.

RECOMMENDATIONS
This study recommends the safe and effec ve applica on of dextrose prolotherapy injec on as an alterna ve treatment module in cases of chronic plantar fascii s.

LIMITATION OF THE STUDY
A few limita ons of the study were: 1. No control group or randomiza on, 2. short-term follow-up 3. A small sample group 4. Lack of specific prolotherapy guidelines