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Viscosupplementation with Hyaluronic Acid or Polynucleotides: Results and Hypothesis for Condro-synchronization
Journal of Clinical Trials

Journal of Clinical Trials
Open Access

ISSN: 2167-0870

+44 20 3868 9735

Research Article - (2014) Volume 4, Issue 6

Viscosupplementation with Hyaluronic Acid or Polynucleotides: Results and Hypothesis for Condro-synchronization

Saggini R1*, Di Stefano A2, Capogrosso F2, Carniel R3, Haidar Hassan K4 and Bellomo RG5
1Neuroscience and Imaging Department, G d Annunzio University, Chieti, Italy, E-mail: [email protected]
2School of Specialties in PRM, G d Annunzio University, Chieti, Italy, E-mail: [email protected]
3Academic School of Specialties in PRM, G d Annunzio University, Chieti, Italy, E-mail: [email protected]
4Annunzio University, Chieti, Italy and Libanese University of Beirut, Italy, E-mail: [email protected]
5Medicine and Science of Ageing Department, G d Annunzio University, Italy, E-mail: [email protected]
*Corresponding Author: Saggini R, Department of Neuroscience and Imaging, G d Annunzio University, Chieti, Italy, Tel: 0039 08713553006 Email:

Abstract

In literature the treatment of rotator cuff syndrome is basically conservative using NSAIDs, cortisone infiltrations and cryotherapy to relieve pain, electroanalgesia, kinesiotherapy to restore the impaired mobility of the joint and strengthen the muscles, physical therapies using energy such as ultrasound, laser, hyperthermia and shock waves. In the case of lack of response to conservative treatment, arthroscopic surgery can be proposed. International literature is unanimous in considering the viscosupplementation as an effective treatment for reducing pain associated with the rotator cuff syndrome and improve joint function. The intra-articular treatment should ideally not only ensure the
mechanical protection of the articular surface, but also rebalance homeostasis of chondrocytes through the restoration of the microenvironment and nutritional supplements of the joint. The aim of this study was to evaluate the efficacy of viscosupplementation with hyaluronic acid and polynucleotides in the treatment of patients with rotator cuff syndrome for incomplete lesion of the supraspinatus. 80 subjects (43 M - 37 F) aged between 40 and 65 years (average age 54) were evaluated and treated. All they suffered from rotator cuff syndrome with incomplete injury of the tendon of the supraspinatus ascertained clinically and by ultrasound examination and MRI. The subjects were randomly divided into 2
groups (A and B). Group A made 4 sessions of infiltrative treatment with hyaluronic acid, once per week. Group B made 4 sessions of infiltrative treatment with infiltrative polynucleotides, 1 time per week. All subjects performed, during the whole period of treatment, upper limb proprioception and joint ROM functional recovery with Multi Joint System (MJS) at a frequency of 3 weekly sessions each one of 45 minutes. The results are comparable in the two groups in terms of improvement in both short and medium term. In view of these evidences we could hypothesize that the association of supplementation of the 2 elements, given together or temporally delayed could be further significant for an additional
maintenance of results in the long term.

Keywords: Chondro-syncronization, Viscosupplementation, Hyluronic acid, Plynucleotides, Shoulder, Pain

Introduction

The upper limbs perform many functions in relation to daily activities and work, which can be done thanks to a considerable range of motion of the shoulder joints, with a cost for their inherent stability [1].

Shoulder pain represents the most common complication. The incidence of shoulder problems range between 7 and 25 cases per thousand visits to the primary care physician [2]. The prevalence in adults under 70 ranges between 7 and 27%, while in more than 70 the prevalence is between 13.2 and 26% [3].

In literature there are many definitions to identify this painful and disabling condition, like for example Duplay syndrome and humeroscapularis periarthritis also called (PHS).

The rotator cuff syndrome is classified by our group into four stages:

• The 1st stage is characterized by edema caused by overuse of the arm above shoulder level in sports and work;

• The 2nd stage is characterized by fibrosis and tendinitis: episodes of inflammation and thickening of the bursa;

• The 3rd stage is characterized by a partial tear of the rotator cuff tendons and with the involvement of the biceps brachii;

• The 4th stage is characterized by at least 2 complete tearing of tendons in the rotator cuff.

In literature the treatment of rotator cuff syndrome is basically conservative using NSAIDs, cortisone infiltrations and cryotherapy to relieve pain, electroanalgesia, kinesiotherapy to restore the impaired mobility of the joint and strengthen the muscles, physical therapies using energy such as ultrasound, laser, hyperthermia and shock waves. In the case of lack of response to conservative treatment, arthroscopic surgery can be proposed [4-7].

International literature is unanimous in considering the viscosupplementation as an effective treatment for reducing pain associated with the rotator cuff syndrome and improve joint function. [8-10].

The viscosupplementation is performed through the intra-articular infiltration of exogenous hyaluronic acid, or its derivatives, in order to restore the rheological properties of the synovial fluid which is also made by lubricina and phospholipids [10]. Hyaluronic acid is able to increase the viscoelastic properties of synovial fluid protecting cartilage from mechanical stress and reducing pain.

The literature agrees that viscosupplementation can be considered a safe and effective therapy [11-13].

It is thought that the analgesic effect of treatment with intraarticular hyaluronic acid may be correlated to several mechanisms which include the reduction of nociceptive stimulation through the production of a elasto-viscous barrier, around the nociceptive afferent fibers in the intracellular matrix [14]. The long-term efficacy of this treatment on symptoms (which ends after a certain time in relation to the effective time of permanence of the product in the joint) may be related to the restoration of the endogenous synthesis of high quality collagen [15].

Literature has also demonstrated the effectiveness of polynucleotides in the treatment of osteoarthritis in comparison to the standard treatment of viscosupplementation with hyaluronic acid with encouraging results [16,17].

The aim of this study was to evaluate the efficacy of viscosupplementation with hyaluronic acid or polynucleotides in the treatment of patients with rotator cuff syndrome for incomplete lesion of the supraspinatus.

Materials and Methods

165 subjects (97 M - 68 F) aged between 40 and 65 years (average age 55) were evaluated and treated. All them suffered from shoulder pain due to rotator cuff syndrome with incomplete injury of the tendon of the supraspinatus ascertained clinically and by ultrasound examination and MRI [18]. The multicenter study was conducted at the D’Annunzio University in Chieti and at the conventioned rehabilitation centers in Conegliano Veneto and Florence.

Inclusion criteria were: age between 40 and 65 years, symptoms of rotator cuff syndrome for at least 6 months, partial-thickness tear of supraspinatus, subacromial artropathy.

Exclusion criteria are: pregnancy, known hypersensitivity to products, infiltrative therapy with hyaluronic acid, polynucleotides or corticosteroids in progress, drug abuse or alcohol abuse, totalthickness tear of supraspinatus, concomitant use of anticoagulants, significant co-morbidities.

During the study period was not allowed corticosteroids or NSAIDs intake.

The subjects were randomly divided into 3 groups (A, B and C).

• Group A made 4 sessions of infiltrative treatment with hyaluronic acid (sodium hyaluronate 40.0 mg - 1100 million Dalton, ©Synovial One, IBSA), once a week.

• Group B made 4 sessions of infiltrative treatment with infiltrative polynucleotides (40 mg of a compound made up of polynucleotides, polymeric molecules which can retrieve large amounts of water and reorganize their structure directing and coordinating water molecules to form a three-dimensional gel, ©Condrotide, BIOFUTURA), once a week;

• Group C made 4 sessions of infiltrative treatment with local anaesthetic (control group) with 0.5 ml of lidocaine 2%, once a week.

Anterior infiltrative approach was used in both groups; the injection site was marked and disinfected with iodine, or with chlorhexidine solution in case of known allergy; all injections were ecoguided [19].

All subjects performed, during the whole period of treatment, upper limb proprioception and joint ROM functional recovery with Multi Joint System (MJS) at a frequency of 3 weekly sessions each one of 45 minutes.

All subjects were evaluated at the beginning of the protocol (T0), at the end of the protocol after 30 days (T1) and at follow-up at 90 (T2) and 120 days (T3) using the VAS scale for measuring the level of subjective pain, specific clinical tests for rotator cuff, Constant Murley Scale (simple standardized method of clinical assessment of shoulder function with a maximum score of 100 points), measurement of shoulder ROM in the movements of flexion and abduction-adduction, Davies isokinetic test to the angular velocity of 90°/sec [20].

Statistical analysis of data was performed using non-parametric t-test for unpaired samples according to Welch. The minimum level for statistical significance was set at P<0.05. The software used for statistical analysis was GraphPad Prism (version 5) (Abacus Concepts GraphPad Software, San Diego, CA).

Results

At time T0 all subjects in both groups had positive Jobe test, a sign of lesion of the supraspinatus; 8 subjects in group A and 5 in group B also showed a positivity to the lift-off test, sign of concomitant involvement of the subscapularis, all subjects showed also positivity to Neer test.

clinical evaluation performed after 30 days (T1), showed negative Jobe test in 37 subjects in group A and 38 subjects in group B; Neer test was negative in all subjects, the lift-off test resulted positive only in 2 subjects in group A and 3 subjects in group B.

In group A after 30 days was found a significant improvement (P<0.01) in the average final score achieved at the Constant Murley Score: by 49 (T0) to 85 at T1 time.

The overall average score in VAS scale for pain in Group A was reduced from 7.72 to 2.11 (p<0.01) at T1; it was also observed an increase of joint ROM with a final average range 0-123° in flexion (T0: 0-88°) and 0-98° in abduction (0°-85°).

Davis isokinetic test showed at T1: increase in the values of the peak of moment of maximum force (Max MdF), both for external rotators (T0 23.1 - 25.1 T1) and intra-rotators (41.5 T0 - T1 45.6).

In group B, after 30 days it was found a significant improvement (P<0.01) in the average final score achieved at the Constant Murley Score: by 48 (T0) to 87 at T1.

The overall average score in VAS scale for pain in Group A was reduced from 8.03 to 2.07 (p<0.01) at T1; it was also observed an increase of joint ROM with a final average range 0-125° in flexion (T0: 0-89°) and 0-97° in abduction (0°-86°).

Davis isokinetic test showed at T1: increase in the values of the peak of moment of maximum force (Max MdF), both for external rotators (T0 23.7 – T1 25.4) and intra-rotators (T0 41.4 – T1 45.6).

In group C, after 30 days was found: no significant improvement in the average final score achieved at the Constant Murley Score (47 (T0) to 49 at T1); a mild but no significant reduction in pain level assessed by VAS (8.05 T0; 5.5 T1); no increase in strength at Davis isokinetic test both in external rotators (T0 23.5 – T1 23.6) and in intra-rotators (T0 40.8 – T1 41); no significant increase in the joint ROM (flexion 0-85 T0 - 0-88 T1; abduction 0-85 T0 – 0-87 T1).

The ultrasound control after 30 days showed significant reduction of the hypoechoic image which was highlighted in the initial evaluation in groups A and B, sign of edema and inflammatory state reduction.

The 90 and 120 days follow-up showed negativity to specific tests for the rotator cuff syndrome and the maintenance of the obtained results in groups A and B as shown in Table 1-4 and Graph 1-4.

VAS T0 T1 (30 days) T2 (90 days) T3 (120 days)
Gr. A 7.72 2.11 2.23 2
Gr. B 8.03 2.07 2.05 1.9
Gr. C 8.05 5.50 7 7.95

Table 1: VAS results in the 3 groups.

ROM AF T0 T1 (30 days) T2 (90 days) T3 (120 days)
Gr. A 0-88 0-123 0-125 0-135
Gr. B 0-89 0-125 0-129 0-137
Gr. C 0-85 0-88 0-91 0-90

Table 2: ROM in flexion.

ROM ABD/ADD T0 T1 (30 days) T2 (90 days) T3 (120 days)
Gr. A 0-85 0-98 0-101 0-110
Gr. B 0-86 0-97 0-103 0-113
Gr. C 0-85 0-87 0-88 0-87

Table 3: ROM in abduction/adduction.

CONSTANT MURLEY SCALE T0 T1 (30 days) T2 (90 days) T3 (120 days)
Gr. A 49 85 88 94
Gr. B 48 87 89 93
Gr. C 47 49 49 49

Table 4: Constant-Murley score results.

clinical-trials-VAS-scale-treatment

Graph 1: Trend in the level of subjective pain of VAS scale after the treatment period and at follow-up at 90 and 120 days.

clinical-trials-Constant-Murley-Scale

Graph 2: Trend of Constant Murley Scale after the treatment period and at follow-up at 90 and 120 days.

clinical-trials-isokinetic-test-extra-rotators

Graph 3: Trend of isokinetic test of extra-rotators after the treatment period and at follow-up at 90 and 120 days.

clinical-trials-isokinetic-Trend-isokinetic-test

Graph 4: Trend of isokinetic test of intra-rotators after the treatment period and at follow-up at 90 and 120 days.

Discussion

A significant reduction in pain and increase in constant score after hyaluronic acid or polynucleotides injection has been described in the results both in the short and medium term (90 and 120 days follow up).

Ideally the intra-articular treatment should not only ensure the mechanical protection of the articular surface, but also rebalance homeostasis of chondrocytes through the restoration of the microenvironment and nutritional supplements of the joint.

Polynucleotides are polymeric molecules which can deeply moisturize the articular surface and are subjected to enzymatic cleavage with progressive intra-articular release both of the water molecules and of the small oligonucleotides (nucleosides, nucleotides, nucleobases), thus maintaining for long time the moisturizing, viscoelastic and metabolic effect [21-23].

Sodium hyaluronate is effective in managing acute or chronic ligaments and tendon injuries HA are believed to integrate into the extracellular fibrin matrix to help realignment of fibrils thanks to electrostatic interactions. Thus, stability of form and function is then restored allowing healing to occur in structures (ligaments and tendons) and shortening the rehabilitation process. Recent research findings demonstrated that repeated periarticular injections of the study materials were more effective in pain relief and joint function improvement, compared to placebo or standard conservative treatment Long-term follow-up by investigators confirmed the therapeutic effects persist after 12 and 24 months. Several trials using sodium hyaluronate in the treatment for chronic shoulder pain have been documented, on shoulder osteoarthritis RC tears, peri-arthritis, adhesive capsulitis, and chronic shoulder pain of different etiologies. The effectiveness of subacromial injections of HA alone in patients with chronic RC tendinopathy is also reported in the literature. In an open label multicenter study, Itokazu et al., [9] observed a significant pain and range of motion improvement after subacromial high-molecular weight sodium hyaluronate injection for 5 weeks or more, and they conclude that this treatment was effective in patients with periarthritis of the shoulder [10].

From the meta-analysis of the literature and our data it appears that is not so much the molecular weight expressed in million Dalton to influence the evolution of treatment, since the amount of hyaluronic acid introduced into the joint cavity in one solution, thus to unleash an action lubricant and anti-inflammatory. We believe that this can be applied even to polynucleotides in order to determine the significant metabolic action.

Conclusion

The chondro-synchronization, through the recovery of the mixture of articular lubrication is the target to be searched in the local therapy of complex joint damage. In view of these evidences we could hypothesize that the association of supplementation of the 2 elements, given together or temporally delayed could be further significant for an additional maintenance of results in the long term.

It might be conceivable that a better treatment could provide for a cycle of alternating introduction of the two substances, ie hyaluronic acid and polynucleotides.

Further studies with a larger series are needed to further clarify methods of administration of the best therapy.

References

  1. van der Windt DA, Koes BW, de Jong BA, Bouter LM (1995) Shoulder disorders in general practice: incidence, patient characteristics, and management. Ann Rheum Dis 54: 959-964.
  2. Luime JJ, Koes BW, Hendriksen IJ, Burdorf A, Verhagen AP, et al. (2004) Prevalence and incidence of shoulder pain in the general population; a systematic review. Scand J Rheumatol 33: 73-81.
  3. Saggini R, Coco V, Di Pancrazio L, Megna M, Iodice P, et al. (2012) Long-Term Results Of Rehabilitative Management With Eswt In Rotator Cuff Disease With Partial Tears. European Journal of Inflammation 10: 483-490.
  4. Saggini R, Iodice P, Cancelli F, Romano V, Di Bonaventura V, et al. (2006) Therapeutic rehabilitative approach in the painful shoulder syndrome with partial tear and calcifying tendinitis of rotator cuff: retrospective analysis. Europa Medicophysica 42: 75-78.
  5. Saggini R, Cavezza T, Di Pancrazio L, Pisciella V, Saladino G, et al. (2010) Treatment of lesions of the rotator cuff. J BiolRegulHomeost Agents 24: 453-459.
  6. Kim YS, Park JY, Lee CS, Lee SJ (2012) Doeshyaluronate injection work in shoulder disease in early stage? A multicenter, randomized, single blind and open comparative clinical study. J Shoulder Elbow Surg 21:722-727.
  7. Penning LI, de Bie RA, Walenkamp GH (2012) The effectiveness of injections of hyaluronic acid or corticosteroid in patients with subacromial impingement: a three-arm randomised controlled trial. J Bone Joint Surg Br 94: 1246-1252.
  8. Merolla G, Bianchi P, Porcellini G (2013) Ultrasound-guided subacromial injections of sodium hyaluronate for the management of rotator cufftendinopathy: a prospective comparative study with rehabilitation therapy. MusculoskeletSurg1: 49-56.
  9. Pozo MA, Balazs EA, Belmonte C (1997) Reduction of sensory responses to passive movements of inflamed knee joints by hylan, a hyaluronan derivative. Exp Brain Res 116: 3-9.
  10. Kwon YW, Eisenberg G, Zuckerman JD(2013) Sodium hyaluronate for the treatment of chronic shoulder pain associated with glenohumeral osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. Shoulder Elbow Surg 22: 584-594.
  11. Costantino C, Olvirri S (2009) Rehabilitative and infiltrative treatment with hyaluronic acid in elderly patients with rotator cuff tears. Acta Biomed 80: 225-229.
  12. Andrews JR (2005) Diagnosis and treatment of chronic painful shoulder: review of nonsurgical interventions. Arthroscopy 21: 333-347.
  13. Bagga H, Burkhardt D, Sambrook P, March L (2006) Longterm effects of intraarticularhyaluronan on synovial fluid in osteoarthritis of the knee. J Rheumatol 33: 946-950.
  14. (2000) Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 43: 1905-1915.
  15. Vanelli R, Costa P, Rossi SMP, Benazzo F (2010) Efficacy of intra-articular polynucleotides in the treatment of knee osteoarthritis: a randomized, double-blind clinical trial. Knee Surg Sports TraumatolArthrosc 18: 901-907.
  16. Penning LI, de Bie RA, Walenkamp GH (2014) Subacromial triamcinolone acetonide, hyaluronic acid and saline injections for shoulder pain an RCT investigating the effectiveness in the first days. BMC MusculoskeletDisord 15: 352.
  17. Lim TK, Koh KH, Shon MS, Lee SW, Park YE, et al. (2014) Intra-articular injection of hyaluronate versus corticosteroid in adhesive capsulitis. Orthopedics 37: e860-865.
  18. Ellenbecker TS, Davies GJ (2000) The application of isokinetics in testing and rehabilitation of the shoulder complex. J Athl Train 35: 338-350.
  19. Saggini R, Di Stefano A, Cavezza T, Saladino G, Bellomo RG (2013) Intrarticular treatment of osteoartropaty knee with polynucleotides: a pilot study with medium-term follow-up. J BiolRegulHomeost Agents 27: 543-549.
  20. Guizzardi S, Galli C, Govoni P, Boratto R, Cattarini G, et al. (2003) Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair. Life Sci 73: 1973-1983.
  21. Muratore O, Cattarini G, Gianoglio S, Tonoli EL, Sacca` SC, Ghiglione D, et al. (2003) A human placental polydeoxyribonucleotide (PDRN) may promote the growth of human corneal fibroblasts and iris pigment epithelial cells in primary cultures. New Microbiol 26:13-26.
Citation: Saggini R, Di Stefano A, Capogrosso F, Carniel R, Haidar Hassan K, et al. (2014) Viscosupplementation with Hyaluronic Acid or Polynucleotides: Results and Hypothesis for Condro-synchronization. J Clin Trials 4:198.

Copyright: © 2014 Saggini R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.