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Research Article|Articles in Press

Effectiveness of proprioceptive neuromuscular facilitation therapy and strength training among post-menopausal women with thumb carpometacarpal osteoarthritis. A randomized trial

Open AccessPublished:August 07, 2022DOI:https://doi.org/10.1016/j.jht.2022.07.005

      Highlights

      • Improvements in disability scores were clinically relevant with both programs.
      • Mobility improved by 29% and pain was reduced by 57% in the combined program.
      • Strength improved in both groups but with a greater effect size in combined program.
      • Improvements in disability, pain, mobility and strength were maintained 1-month later.

      ABSTRACT

      Background

      Thumb carpometacarpal osteoarthritis (CMC OA) greatly affects post-menopausal women. It is characterized by pain and functional deficits that limit the performance of activities of daily life and affect quality of life.

      Purpose

      Analyze the effects of 4/weeks strength training, with and without proprioceptive neuromuscular facilitation (PNF) on the disability among post-menopausal women with thumb CMC OA. Secondly, analyze the effects on pain, mobility, and strength.

      Study Design

      Superiority randomized clinical trial.

      Methods

      42 women were randomly allocated to strength training program (SEG, n = 21) and to a strength training plus PNF therapy program (PNFG, n = 21). The Disability (disabilities of the arm, shoulder and hand questionnaire), pain (visual analogue scale), mobility (Kapandji Test), and hand strength were evaluated pre, post intervention (at 4 weeks) and follow-up (at 8 weeks).

      Results

      Disability was significantly reduced in both groups after intervention, but reduction was statistically superior in PNFG (between-group mean difference [MD] = -16.69 points; CI = -21.56:-11.82; P<.001; d = 2.14). Similar results were observed for secondary outcomes: pain (MD = -2.03; CI = -2.83:-1.22; P<.001; d = 1.58), mobility (MD = 0.96; CI = 0.52:1.38; P<.001; d = 1.40) and strength (grip: MD = 3.47kg; CI = 1.25:5.69; P = .003; d = 0.97, palmar: MD = 0.97kg; CI = 0.14:1.80; P = .024; d = 0.72, tip: MD = 1.12kg; CI = 0.41:1.83; P = .003; d = 0.99 and key pinch: MD = 0.85kg; CI = 0.001:1.70; P = .049; d = 0.62). These improvements were maintained at follow-up.

      Conclusions

      The combination of PNF exercises and strength training is more effective for reducing disability pain and improve mobility and strength in post-menopausal women with CMC OA than a programme based solely on strength.

      Keywords

      Introduction

      Thumb carpometacarpal osteoarthritis (CMC OA) presents with localized pain at the base of the thumb, restricted thumb mobility, and muscle weakness. It is one of the most common causes of upper limb-related disability in Europe and the United States.
      • Schopflocher D
      • Taenzer P
      • Jovey R.
      The prevalence of chronic pain in Canada.
      • Lee HJ
      • Paik N-J
      • Lim J-Y
      • Kim KW
      • Gong HS.
      The impact of digit-related radiographic osteoarthritis of the hand on grip-strength and upper extremity disability.
      • Murphy L
      • Helmick CG.
      The impact of osteoarthritis in the United States: a population-health perspective: a population-based review of the fourth most common cause of hospitalization in U.S. adults.
      • Carmona L
      • Episer G de E
      • Laffon A
      • Ballina J
      • Gabriel R.
      Proyecto EPISER 2000: prevalencia de enfermedades reumáticas en la población española. metodología, resultados del reclutamiento y características de la población.
      CMC OA has a higher incidence in women than men
      • Sodha S
      • Ring D
      • Zurakowski D
      • Jupiter JB.
      Prevalence of osteoarthrosis of the trapeziometacarpal joint.
      • Haara MM
      • Heliövaara M
      • Kröger H
      • et al.
      Osteoarthritis in the carpometacarpal joint of the thumb prevalence and associations with disability and mortality.
      and this increases exponentially in post-menopausal women.
      • Haara MM
      • Heliövaara M
      • Kröger H
      • et al.
      Osteoarthritis in the carpometacarpal joint of the thumb prevalence and associations with disability and mortality.
      • Pai S
      • Talwalkar S
      • Hayton M.
      Presentation and management of arthritis affecting the trapezio-metacarpal joint.
      Between the ages of 50 and 60, it affects over 66% of women, becoming a highly prevalent disease.
      • Pai S
      • Talwalkar S
      • Hayton M.
      Presentation and management of arthritis affecting the trapezio-metacarpal joint.
      • Wilder FV
      • Barrett JP
      • Farina EJ.
      Joint-specific prevalence of osteoarthritis of the hand.
      The symptoms affect the women's ability to perform certain daily living activities such as opening a jar, turning a key in a lock, opening food packets, and wringing out laundry.
      • Lee HJ
      • Paik N-J
      • Lim J-Y
      • Kim KW
      • Gong HS.
      The impact of digit-related radiographic osteoarthritis of the hand on grip-strength and upper extremity disability.
      ,
      • Kjeken I
      • Dagfinrud H
      • Slatkowsky-Christensen B
      • et al.
      Activity limitations and participation restrictions in women with hand osteoarthritis: patients’ descriptions and associations between dimensions of functioning.
      • Faour-Martín O
      • Martín-Ferrero MÁ
      • Valverde-García JA
      • Vega-Castrillo A
      • De La
      • Red-Gallego MÁ.
      Rhizarthrosis fourth grade of eaton with hyperextension of the metacarpophalangeal joint.
      • Bertozzi L
      • Valdes K
      • Vanti C
      • Negrini S
      • Pillastrini P
      • Villafañe JH.
      Investigation of the effect of conservative interventions in thumb carpometacarpal osteoarthritis: systematic review and meta-analysis.
      The main objective in the management of CMC OA should focus on controlling the symptoms, optimizing the functionality of the hand to favor the performance of daily living activities, and improving quality of life. For symptom management, there are 2 types of treatment for thumb CMC OA: surgery and conservative therapy.
      • Berggren M
      • Joost-Davidsson A
      • Lindstrand J
      • Nylander G
      • Povlsen B.
      Reduction in the need for operation after conservative treatment of osteoarthritis of the first carpometacarpal joint: a seven-year prospective study.
      ,
      • O'Brien VH
      • Giveans MR.
      Effects of a dynamic stability approach in conservative intervention of the carpometacarpal joint of the thumb: a retrospective study.
      There are different treatment modalities that should be considered. Pharmacological strategies include analgesic and anti-inflammatory drugs or intra-articular injections of glucocorticoids (in special cases such as patients with active joint inflammation due to a flare-up of the disease), then there are also non-pharmacological alternatives (the use of orthoses, manual therapy and exercise programmes),
      • Kjeken I
      • Smedslund G
      • Moe RH
      • Slatkowsky-Christensen B
      • Uhlig T
      • Hagen KB.
      Systematic review of design and effects of splints and exercise programs in hand osteoarthritis.
      • Villafañe JH
      • Cleland JA
      Fernández-de-Las-Peñas C. The effectiveness of a manual therapy and exercise protocol in patients with thumb carpometacarpal osteoarthritis: a randomized controlled trial.
      and surgery. The latter option should be considered when the other strategies have not been effective at reducing the pain. The decision on the type of treatment must be a consensus between the patient and the health professional in which the individual factors of the patient (eg age, level of pain), the degree of affectation of the structure, comorbidities, and expectations are assessed.
      • Kamaruzaman H
      • Kinghorn P
      • Oppong R.
      Costeffectiveness of surgical interventions for the management of osteoarthritis: a systematic review of the literature.
      • Wouters RM
      • Vranceanu A-M
      • Slijper HP
      • et al.
      Patients with thumb-base osteoarthritis scheduled for surgery have more symptoms, worse psychological profile, and higher expectations than nonsurgical counterparts: a large cohort analysis.
      • Spaans AJ
      • van Minnen LP
      • Kon M
      • Schuurman AH
      • Schreuders ART
      • Vermeulen GM.
      Conservative treatment of thumb base osteoarthritis: a systematic review.
      • Kloppenburg M
      • Kroon FP
      • Blanco FJ
      • et al.
      update of the EULAR recommendations for the management of hand osteoarthritis.
      The results obtained by the clinical trials on the effect of exercise on CMC OA-derived symptomatology are positive.
      • Østerås N
      • Kjeken I
      • Smedslund G
      • et al.
      Exercise for hand osteoarthritis: a cochrane systematic Review.
      • Villafañe JH
      • Valdes K
      • Pedersini P
      • Berjano P.
      Thumb carpometacarpal osteoarthritis: a musculoskeletal physiotherapy perspective.
      However, its prescription is not well-described and it is not always recommended. While the guidelines of the European League Against Rheumatism (EULAR),
      • Kroon FP
      • Carmona L
      • Schoones JW
      • Kloppenburg M.
      Efficacy and safety of non-pharmacological, pharmacological and surgical treatment for hand osteoarthritis: a systematic literature review informing the 2018 update of the EULAR recommendations for the management of hand osteoarthritis.
      • Zhang W
      • Doherty M
      • Leeb BF
      • et al.
      EULAR evidence based recommendations for the management of hand osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).
      recommend hand exercise therapy, the American College of Rheumatology (ACR) does not include therapeutic exercise within its clinical guidelines for this pathology.
      • Hochberg MC
      • Altman RD
      • April KT
      • et al.
      American college of rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee.
      Furthermore, the methodological quality according to the various reviews needs to be improved, thus more research is needed in this area.
      • Østerås N
      • Kjeken I
      • Smedslund G
      • et al.
      Exercise for hand osteoarthritis: a cochrane systematic Review.
      ,
      • Moe RH
      • Kjeken I
      • Uhlig T
      • Hagen KB.
      There is inadequate evidence to determine the effectiveness of nonpharmacological and nonsurgical interventions for hand osteoarthritis: an overview of high-quality systematic reviews.
      Furthermore, in spite of that, CMC OA is one of the most common forms of hand OA affecting post-menopausal women. To our knowledge, there are no specific exercise programmes for post-menopausal women providing comprehensive details of the training parameters (number of sessions per week, duration of the sessions, detailed description of the exercises, number of repetitions, rests, etc).
      • Bertozzi L
      • Valdes K
      • Vanti C
      • Negrini S
      • Pillastrini P
      • Villafañe JH.
      Investigation of the effect of conservative interventions in thumb carpometacarpal osteoarthritis: systematic review and meta-analysis.
      Ligamentous laxity, joint compression, and a lack of neuromuscular control are the consequences of CMC OA. For this reason, exercise programs should include exercises for neuromuscular control and the strengthening of the stabilizer muscles of the thumb to improve the functionality of the hand.
      • Bertozzi L
      • Valdes K
      • Vanti C
      • Negrini S
      • Pillastrini P
      • Villafañe JH.
      Investigation of the effect of conservative interventions in thumb carpometacarpal osteoarthritis: systematic review and meta-analysis.
      ,
      • Villafañe JH
      • Valdes K
      • Pedersini P
      • Berjano P.
      Thumb carpometacarpal osteoarthritis: a musculoskeletal physiotherapy perspective.
      These types of exercise are the basis of proprioceptive neuromuscular facilitation (PNF). PNF or the Kabat concept, also known as sensorimotor reprogramming, is defined as a technique that uses the sensory stimulation of both a superficial type (tactile) and deep type (joint positions or myotendinous stretch) to improve functional movements by facilitating and inhibiting the muscle groups. The therapist uses patterns of diagonal movement (abduction-adduction, flexion-extension) and spiral movement (rotation) to enable the patient to achieve the highest level of functionality.
      • Smedes F
      • Heidmann M
      • Schäfer C
      • Fischer N
      • Stępień A
      The proprioceptive neuromuscular facilitation-concept; the state of the evidence, a narrative review.
      This method has been used as a therapeutic intervention in the treatment of pain and functionality of different joints. The results show that PNF significantly reduces pain and improves functionality.
      • Shimura K
      • Kasai T.
      Effects of proprioceptive neuromuscular facilitation on the initiation of voluntary movement and motor evoked potentials in upper limb muscles.
      • Song Q
      • Shen P
      • Mao M
      • Sun W
      • Zhang C
      • Li L.
      Proprioceptive neuromuscular facilitation improves pain and descending mechanics among elderly with knee osteoarthritis.
      • Birinci T
      • Razak Ozdincler A
      • Altun S
      • Kural C
      A structured exercise programme combined with proprioceptive neuromuscular facilitation stretching or static stretching in posttraumatic stiffness of the elbow: a randomized controlled trial.
      • Balcı NC
      • Yuruk ZO
      • Zeybek A
      • Gulsen M
      • Tekindal MA.
      Acute effect of scapular proprioceptive neuromuscular facilitation (PNF) techniques and classic exercises in adhesive capsulitis: a randomized controlled trial.
      • Çelik MS
      • Sönmezer E
      • Acar M.
      Effectiveness of proprioceptive neuromuscular facilitation and myofascial release techniques in patients with subacromial impingement syndrome.
      However, to our knowledge, no clinical trials have been conducted in post-menopausal women with thumb CMC OA.
      Taking into account the lack of studies designed specifically looking into post-menopausal women, the primary objective of this study was to analyze the effects of strength training with and without proprioceptive neuromuscular facilitation therapy on the disability among post-menopausal women with thumb CMC OA. Secondly, we have explored the effects on pain, mobility, and strength. We hypothesized that muscle strengthening combined with a neuromuscular facilitation therapy programme would provide greater benefits compared to strength training alone.

      Methods

      Trial design

      A randomized superiority clinical trial involving the sampling of consecutive cases was carried out from September 2013 to May 2015 in terms of patient recruitment. The participants were randomly allocated to 2different groups using a simple (blocks number were not used) randomization sequence generation using the SPSS version 22.0 statistical program via an external assistant who was blinded to the study objectives. There was the strength training group (SEG) that received exclusively strength training and the neuromuscular facilitation group (PNFG) who received the same plus a proprioceptive exercise. The allocation ratio was 1:1 and for the allocation of the enrolled participants, a randomly ordered list was used. To reduce bias, the physical therapist who performed the assessments and the statistician were both unaware of the group allocation. In relation to the women who participated, they all received the same information: they would carry out a physiotherapy program consisting of a therapeutic exercise program 3 times a week for a month. They didn't know if their exercise program was just about strength or whether it included both strength and proprioception.
      All participants were informed in advance about the purpose and content of this research. Written informed consent was obtained from all individual participants. The study conformed to the Declaration of Helsinki, and has been approved by the Ethics Committee of the University of Valencia under registration number H1366799480593.

      Participants

      Forty-six women diagnosed with thumb CMC OA volunteered to participate in this study. They were recruited from several clinics and hospitals in Valencia. The inclusion criteria were as follows: post-menopausal women over 18 years old diagnosed with thumb CMC OA stage ≤ 3 on the Eaton-Littler Burton classification
      • Kennedy CD
      • Manske MC
      • Huang JI.
      Classifications in brief: the eaton-littler classification of thumb carpometacarpal joint arthrosis.
      according to a clinical and radiological examination. The exclusion criteria were women who had previously received surgery for CMC OA and women with cognitive alterations that prevented them from carrying out the performance of the proposed exercises. This was as well as women who had received hormone replacement therapy and those who ingested cartilage, calcium or vitamin D supplements, who were excluded. To detect whether cognitive alterations were present or not, it was verified through their medical history that the patients did not present with any neurological problems or legal incapacitations. Also, during the signing of the consent form, it was determined that they were autonomous women who were able to respond to the indications proposed by the evaluator. The participation of women who had radiologically confirmed lesions was not considered. The participants were instructed to not begin any new physical therapy or medical treatment during the month of the intervention and during the training sessions. They were asked this weekly to check that there were no changes in treatment.

      Intervention

      As reported, the participants were allocated to 1 of the 2 different intervention groups. Treatments were applied by one physiotherapist with more than 10 years experience in physical treatment. During the intervention period, the participants followed their usual treatment regimen. None of them required the use of orthoses.

      Strength training group (SEG)

      The SEG performed a 4-week strength training programme. This programme included warm-up exercises focused on joint mobility and strength training at a frequency of 3 sessions per week (a total of 12 sessions). All sessions took place on Mondays, Wednesdays, and Fridays between 09:00 and 11:00 AM, lasting 30 minutes each (Table 1).
      Table 1Strength and proprioceptive training
      1. WARM-UP EXCERCISE (SEG AND PNFG)

      Patient position: sitting, elbow at 90°, forearm supported on the stretcher with neutral pronosupination.

      Generalized joint mobility exercises: (10 repetitions of each exercise with a 1-min rest between each set):

      Wrist flexion-extension

      Flexion-extension of metacarpophalangeal joints

      Flexion-extension of interphalangeal joints
      2. STRENGTH TRAINING (SEG AND PNFG)

      Patient position: supine position, shoulder in 30° abduction, elbow in 9° flexion and resting on the stretcher, forearm in neutral pronosupination.

      3 sets of 10 repetitions each, with a 60-s break between sets and a 30-s rest between repetitions (between exercises). Contractions (5 s) against maximum resistance: the Squeeze Eggs material was used
      Grip Pinch: open and close fingersFigure 2a Figure 2b
      Palmar Pinch: opposition of the thumb with the distal phalanges of the other fingersFigure 2c

      Figure 2d
      Key Pinch: opposition of the thumb with the side face of the second phalanx of the second fingerFigure 2e

      Figure 2f
      3. PNF EXERCISES (PNFG ONLY)

      Patient position: supine position, shoulder in 30° abduction, elbow in 90° flexion and resting on the stretcher, forearm in neutral prono-supination.

      PNF pattern used: hand variation A-B and B-A. In this variation the participant must perform a flexion, adduction and opposition movement that will be resisted in an isometric way by the physiotherapist. After 5 s of contraction, you will need to extend and abduct your thumb.

      Technique used: rhythmic stabilization: alternate isometric contractions against resistance, the physiotherapist resists the contraction of the agonist muscle group and after 5 s contraction, to resist the antagonist muscle group, again resisting for 5 seconds.

      3 sets of 15 repetitions each, with a 60-s break between sets and a 30-s rest between repetitions (between exercises).

      Hand position of the physiotherapist: Pattern: A-B: fingers extended over the thenar and hypothenar eminence.

      Hand position of the physiotherapist: Pattern: B-A: hand of the physiotherapist on the anterior face of 1/3 distal of the forearm.
      SEG: strength training group PNFG: proprioceptive neuromuscular facilitation group; PNF: proprioceptive neuromuscular facilitation

      Proprioceptive neuro-facilitation group (PNFG)

      The PNFG performed the same warm-up and strength training as the SEG in addition to a programme based on rhythmic stabilization for the thumb. Three sessions were performed per week, on Mondays, Wednesdays and Fridays, totaling 12 sessions. All sessions took place between 09:00 and 11:00 AM, lasting 45 minutes each (Table 1).

      Outcomes

      Measurements were taken at baseline (T0), at 4 weeks (T1), and at 8 weeks (follow-up, 4 weeks after finishing the training programmes; T2) during which time the participants in both groups performed their customary daily living activities.
      The effects of the interventions on the variables of disability (disabilities of the arm, shoulder, and hand questionnaire: DASH), on the pain perceived (visual analogue scale: VAS), on mobility (oppositional movement of the thumb; Kapandji Test), and on hand strength were assessed. The tests were performed by an external evaluator who was unaware of the participant's treatment group. The assessment was carried out following the protocol of the American Society of Hand Therapists.
      • MacDermid J.
      Clinical Assessment Recommendations.

      Primary outcome: Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH)

      The Spanish version of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire
      • Hervás MT
      • Navarro Collado MJ
      • Peiró S
      • Rodrigo Pérez JL
      • López Matéu P
      • Martínez Tello I.
      Versión española del cuestionario DASH. Adaptación transcultural, fiabilidad, validez y sensibilidad a los cambios [Spanish version of the DASH questionnaire. Cross-cultural adaptation, reliability, validity and responsiveness].
      was used, which is a specific instrument for measuring the disability caused by upper limb conditions. DASH consists of 30 items and 2 modules that are optional, with 4 items each. Each item is scored from 1 to 5 with the values increasing depending on the intensity of the symptoms. The item scores are added to obtain a total score which can range from 30 and 150 points. This becomes a scale of 0 (best possible score) to 100 (worst score possible). DASH showed excellent results in terms of the internal consistency for rheumatoid arthritis (Cronbach's alpha = 0.97)
      • Raven EE
      • Haverkamp D
      • Sierevelt IN
      • et al.
      Construct validity and reliability of the disability of arm, shoulder and hand questionnaire for upper extremity complaints in rheumatoid arthritis.
      and test-retest (r = 0.96).
      • Hervás MT
      • Navarro Collado MJ
      • Peiró S
      • Rodrigo Pérez JL
      • López Matéu P
      • Martínez Tello I.
      Versión española del cuestionario DASH. Adaptación transcultural, fiabilidad, validez y sensibilidad a los cambios [Spanish version of the DASH questionnaire. Cross-cultural adaptation, reliability, validity and responsiveness].

      Secondary outcomes

      Pain (VAS)

      The intensity of perceived pain at rest was measured using a 10-cm visual analogue scale (VAS) whose reliability and validity has been previously reported for chronic pain. The VAS consisted of a horizontal continuous line on which the participants rated their perceived pain intensity, with 0 being “no pain” and 10 being maximum tolerable pain.
      • Haefeli M
      • Elfering A.
      Pain assessment.

      Mobility: oppositional movement of the thumb. Kapandji Test

      The Kapandji score was used to assess the opposition of the thumb. The patients had to touch the following with the distal phalanx of their thumb: the radial side of the proximal phalanx of the index finger, the radial side of the middle phalanx of their index finger, the tip of their index finger, the tip of their middle finger, the tip of their ring finger, the tip of their little finger, the distal interphalangeal joint crease of their little finger, the proximal interphalangeal joint crease of their little finger, the metacarpophalangeal joint crease of their little finger, and the distal palmar crease. The score ranged from 1 to 10. The higher the score, the better the results.
      • Kapandji A.
      Clinical test of apposition and counter-apposition of the thumb.

      Strength

      Isometric grip strength was measured using the SAEHAN Hydraulic Hand Dynamometer (MSD Europe BVBA, Londerzeel – Belgium). The assessment of the various pinch styles was carried out using the SAEHAN Hydraulic Pinch Gauge (MSD Europe BVBA, Londerzeel - Belgium – Europe). This device measures the isometric strength of 3 types of pinch: palmar pinch (between the thumb, index, and middle fingers), tip pinch (thumb tip to the index fingertip), and key pinch (the thumb pad to the lateral aspect of the middle phalanx of the index finger). The participants performed 3 repetitions of isometric contractions lasting 5 seconds. There was a 60 second break to avoid muscle fatigue.
      • Mathiowetz V
      • Kashman N
      • Volland G
      • Weber K
      • Dowe M
      • Rogers S.
      Grip and pinch strength: normative data for adults.

      Sample size

      G-Power version 3.1 was used for a priori sample size calculation (Institute for Experimental Psychology, University of Düsseldorf, Düsseldorf, Germany). The sample size was estimated based on the inclusion of 2 study groups measured at 3 time points, expecting a medium effect size (d = 0.5) for the primary outcome (DASH). Furthermore, with a type I error of 5% and a type II error of 10%, a minimum sample size of 36 participants (18 in each group) was required. Finally, a 10% risk of drop-out rate was included in the estimation, with 40 women being the final sample size.

      Statistical methods

      Statistical analyses were performed using the IBM SPSS software (version 26.0; IBM Corp, Armonk, NY, USA). The normality of the data was checked using the Kolmogorov–Smirnov test. The results are shown according to the mean and standard deviation. The anthropometric data from both groups was compared using the independent t-test and Chi-square (χ2) test.
      To evaluate the effect of the interventions on the variables, as well as the data from DASH, VAS, and Kapandji, and the variables of grip, palmar, key and tip pinch in both groups, mixed ANOVA was used (Time [T0, T1 and T2] x Group [SEG and PNFG]) with repeated measures for the time factor. The ANOVA p results were interpreted as follows: p0 indicates between-group differences; p1 indicates within-group differences at T0 and T1; p2 shows the within-group differences at T0 and T2 and p3 shows the within-group differences at T1 and T2. The Bonferroni correction was applied to avoid type I errors in the multiple comparisons when the ANOVA analysis indicated significant differences. Effect size (Cohen d and η2p) was interpreted as small (d = 0.2; η2p = 0.01), medium (d = 0.5; η2p = 0.06) and large (d > 0.8; η2p > 0.14). Differences whose probability of being due to chance of less than 5% (P < .05) were accepted as significant.

      Results

      Participants

      A total of 46 women were assessed for eligibility, 3 failed to meet the inclusion criteria, and 1 declined to participate. Accordingly, the 42 final participants were randomized and all of them completed the study (SEG = 21; PNFG = 21). Participant attendance in both the SEG and PNFG was 100%. No incidents or harm were reported at any time during the interventions (Fig. 1).
      Fig. 1
      Fig. 1Flowchart according to CONSORT Statement for the Report of randomized trials.
      The demographic and clinical characteristics for both groups at baseline are described in Table 2. No significant differences were found, so the study groups were determined to be comparable in terms of age and the time of menopause.
      Table 2Intervention groups at baseline
      SEG (N = 21)PNFG (N = 21)P [95% CI]
      Age (y)61.04 (6.11)59.14 (8.05).39 [-2.55:6.37]
      Menopause (y)48.86 (2.92)48.83 (4.90)-.99 [-2.68:2.73]
      Hand dominance,L/R12(57.1%) / 9 (42.9%)9(42.9%) / 12 (57.1%)χ
      • Lee HJ
      • Paik N-J
      • Lim J-Y
      • Kim KW
      • Gong HS.
      The impact of digit-related radiographic osteoarthritis of the hand on grip-strength and upper extremity disability.
       = 0.85; P = .35
      Eaton Class 13 (14.3%)5 (23.8%)
      Eaton Class 214 (66.7%)14 (66.7%)χ
      • Lee HJ
      • Paik N-J
      • Lim J-Y
      • Kim KW
      • Gong HS.
      The impact of digit-related radiographic osteoarthritis of the hand on grip-strength and upper extremity disability.
       = 1.16; P = .55
      Eaton Class 34 (19%)2 (14.3%)
      Note. Data are expressed as mean (standard deviation). SEG = strength training group; L/R = left/right; PNFG = proprioceptive neuromuscular facilitation group; P = significance; CI = confidence interval; χ2 = chi-square.
      Table 3 shows the results of the main effects obtained through the ANOVA analyses. Statistically significant effects were obtained for the time and group factors, as well as on the time-by-group interaction for all variables except for the palmar pinch and key pinch in the group factor.
      Table 3Main effects result for the ANOVA models
      DASHVASKapandji testGrip pinchPalmar pinchPinch typeKey pinch
      EFFECT TIMEFF(1.48; 59.34) = 100.66F(1.38; 55.16) = 110.00F(1.47; 58.7) = 146.92F(1.52; 60.66) = 83.96F(2; 80) = 77.00F(1.61; 64.38) = 77.64F(2; 80) = 123.37
      P<.001<.001<.001<.001<.001<.001<.001
      η20.7160.7330.7860.6770.6580.6600.755
      EFFECT GROUPFF(1; 40) = 30.36F(1; 40) = 11.24F(1; 40) = 15.12F(1; 40) = 4.25F(1; 40) = 3.77F(1; 40) = 6.22F(1; 40) = 3.19
      P<.001.002<.001.046.059<.0010.082
      η20.4320.2190.2740.0960.0860.1340.074
      INTERACTION EFFECTFF(1.48; 59.34) = 40.71F(1.38; 55.16) = 62.32F(1.47; 58.7) = 26.85F(1.52; 60.66) = 49.23F(2; 80) = 33.91F(1.61; 64.38) = 77.64F(2; 80) = 41.60
      P<.001<.001<.001<.001<.001<.001<.001
      η20.5040.6090.4020.5520.4590.4960.510
      VAS = visual analogue scale; DASH = disabilities of the arm shoulder and hand; P = significance; η2 ETA Square = effect size; F = statistical F.

      Effectiveness of the treatment

      The results of the variables related to disability, pain, and mobility are shown in Table 4. It is noted that at baseline (T0), no significant differences were found between PNFG and SEG in any of the variables analysed.
      Table 4Comparison of disability, pain and mobility variables for the SEG and PNFG groups in pre- (T0), post-intervention (T1) and follow-up (T2)
      T0T1T2Within-group differences
      Mean [95% CI] p1 (T1-T0); dMean [95% CI] p2 (T2-T0); dMean [95% CI] p3 (T2-T1); d
      DASHPNFG34.76 (13.34)14.41 (7.58)11.71 (7.38)-20.34 [-24.48:-16.21] <.001; 1.88-23.05 [-27.73:-18.36] <.001; 2.14-2.71 [-5.09:-0.32] 0.022; 0.36
      SEG37.74 (8.72)31.11 (8.04)33.89 (8.60)-6.63 [-10.76:-2.49] 0.001; 0.75-3.85 [-8.54:0.84] .14; -2.78 [0.39:5.16] 0.018; 0.33
      Between-group differences Mean [95% CI] p0; d-2.98 [-10.00:4.05] 0.40; --16.69 [-21.56:-11.82] <0.001; 2.14-22.18 [-27.17:-17.18] <0.001; 2.77
      VASPNFG5.91 (2.22)2.54 (1.64)2.37 (1.41)-3.37 [-3.92:-2.83] <0.001; 1.74-3.55 [-4.24:-2.85] <0.001; 1.90-0.18 [-0.51:0.16] 0.48
      SEG5.26 (0.85)4.57 (0.79)4.94 (0.89)-0.70 [-1.24:-0.15] 0.009; 0.84-0.32 [-1.02:0.37] 0.59; -0.37 [0.40:0.71] 0.024; 0.44
      Between-group differences Mean [95% CI] p0; d0.65 [-0.40:1.70] 0.22; --2.03 [-2.83:-1.22] <0.001; 1.58-2.58 [-3.31:-1.84] <0.001; 2.18
      Kapandji TestPNFG7.48 (1.12)9.67 (0.48)9.67 (0.58)2.19 [1.76:2.63] <0.001; 2.542.19 [1.75:2.63] <0.001; 2.460.00 [-0.22:0.22] 1; -
      SEG7.43 (0.87)8.71 (0.84)8.05 (0.92)1.29 [0.85:1.72] <0.001; 1.500.62 [0.18:1.06] 0.003; 0.69-0.67 [-0.89:-0.45] <0.001; 0.75
      Between-group differences Mean [95% CI] p0; d0.05 [-0.58:0.67] 0.88; -0.96 [0.52:1.38] <0.001; 1.401.62 [1.14:2.10] <0.001; 2.11
      Data are expressed as mean (standard deviation).
      Statistically significant values are shown in bold.
      SEG = strength training group; PNFG = proprioceptive neuromuscular facilitation group; VAS = visual analogue scale; DASH = disabilities of the arm shoulder and hand; P = significance. CI = confidence interval of the mean difference; D = Cohen's d effect size; T0 = pre-intervention; T1 = post-intervention; T2 = after 1 month of the intervention; p0 = between-group differences; p1 = within-group differences between T1 and T0; p2 = within-group differences between T2 and T0; p3 = within-group differences between T2 and T1.
      The within-group analysis of the DASH variable confirmed that after the intervention (T1), both groups significantly decreased their scores on that scale. Additionally, at the follow-up (T2), PNFG showed a further decrease in score compared to T1. The data of the results between the groups showed that after the intervention, the score was statistically lower both at T1 and T2 in PNFG.
      The intra-group analysis showed that the pain decreased significantly following the intervention (T1) in both groups. This improvement was maintained at follow-up (T2) only for PNFG. In addition, the between group analyses showed that the pain was significantly lower at both T1 and T2 in the PNFG compared to SEG with a large effect size.
      The results of the Kapandji test within the groups showed that mobility increased significantly in both PNFG and SEG after the intervention (T1). However, this improvement was maintained over time (T2) only in PNFG without significant changes between T2 and T1. At the between-group level, the improvement in mobility was statistically greater in PNFG at both T1 and T2, with a large effect size both times.
      Table 5 describes the results of the strength variable in each of its modalities: grip, palmar, tip, and key pinch. It was noted at baseline (T0) that no significant differences were found between the groups for any of the strength variables, whereby both groups showed similar levels of muscle strength. The intra-group analysis showed that both groups significantly improved in strength after the intervention (T1), with this improvement being maintained in the follow-up (T2) only in PNFG. The results between groups confirmed that at both T1 and T2, the strength was statistically greater in PNFG than in SEG for the grip, tip, and key pinch modalities.
      Table 5Comparison of strength variables for the SEG and PNFG groups in pre (T0)-, post-intervention (T1) and follow-up (T2)
      T0T1T2Within-group differences
      Mean [95% CI] p1 (T1-T0); dMean [95% CI] p2 (T2-T0); dMean [95% CI] p3 (T2-T1); d
      Grip Pinch (kg)PNFG14.05 (5.22)19.24 (3.71)19.14 (3.76)5.19 [4.17:6.21] <0.001; 1.155.10 [4.00:6.19] <0.001; 1.12-0.10 [-0.67:0.48] 0.97; -
      SEG14.69 (2.90)15.77 (3.41)14.98 (3.34)1.08 [0.06:2.09] 0.035; 0.340.29 [-0.80:1.38] 0.88; --0.79 [-1.36:-0.21] 0.004; 0.23
      Between-group differences Mean [95% CI] p0; d-0.64 [-3.28:1.99] 0.63; -3.47 [1.25:5.69] 0.003; 0.974.16 [1.95:6.38] <0.001; 1.17
      Palmar Pinch (kg)PNFG2.30 (1.28)4.02 (1.58)4.15 (1.57)1.72 [1.37:2.07] <0.001; 1.201.85 [1.48:2.22] <0.001; 1.290.13 [-0.22:0.47] 0.74; -
      SEG2.50 (1.00)3.06 (1.02)2.73 (1.05)0.55 [0.20:0.91] 0.001; 0.550.23 [-0.14:0.60] 0.220; --0.32 [-0.67:0.02] 0.07; -
      Between-group differences Mean [95% CI] p0; d-0.20 [-0.91:0.51] 0.58; -0.97 [0.14:1.80] 0.024; 0.721.42 [0.59:2.25] 0.001; 1.06
      Tip Pinch (kg)PNFG1.89 (0.91)3.87 (1.36)3.96 (1.38)1.99 [1.56:2.41] <0.001; 1.712.08 [1.62:2.53] <0.001; 1.770.09 [-0.17:0.35] 0.78; -
      SEG2.26 (0.74)2.75 (0.86)2.48 (0.89)0.50 [0.07:0.92] 0.018; 0.610.22 [-0.24:0.68] 0.56; --0.28 [-0.54:-0.01] 0.036; 0.31
      Between-group differences Mean [95% CI] p0; d-0.37 [-0.88:0.15] 0.15; -1.12 [0.41:1.83] 0.003; 0.991.49 [0.76:2.21] <0.001; 1.28
      Key Pinch (kg)PNFG3.70 (1.41)5.55 (1.64)5.53 (1.46)1.85 [1.50:2.19] <0.001; 1.211.83 [1.53:2.14] <0.001; 1.28-0.02 [-0.31:0.28] 1.00; -
      SEG3.88 (1.04)4.70 (1.01)4.11 (1.13)0.81 [0.47:1.16] <0.001; 0.800.23 [-0.07:0.54] 0.17; --0.58 [-0.87:-0.29] <0.001; 0.55
      Between-group differences Mean [95% CI] p0; d-0.18 [-0.96:0.60] 0.64; -0.85 [0.001:1.70] 0.049; 0.621.42 [0.60:2.24] <0.001; 1.09
      Data are expressed as mean (standard deviation).
      Statistically significant values are shown in bold.
      SEG = strength training group; PNFG = proprioceptive neuromuscular facilitation group; p = significance; CI = confidence interval of the mean difference; d = Cohen's d effect size; T0 = pre-intervention; T1 = post-intervention; T2 = after 1 month of the intervention; p0 = between-group differences; p1 = within-group differences between T1 and T0; p2 = within-group differences between T2 and T0; p3 = within-group differences between T2 and T1.

      Discussion

      This study analysed the effectiveness of a programme combining neuromuscular facilitation and strength training versus an exclusively strength training programme in post-menopausal women with thumb CMC OA regarding disability, pain, mobility, and strength. As shown by our results, after both interventions, the degree of disability and perceived pain decreased. There was also an improvement in mobility and strength (in all modes: grip, palmar, tip and key pinch). However, as we hypothesized, the intervention program that combined strength exercises and PNFG exercises showed a significantly greater improvement. To our knowledge, this is the first study to date that has carried out a programme in which post-menopausal women exclusively participated. This is why the results obtained can hardly be compared with those of other studies.
      The DASH questionnaire is a tool designed to evaluate disorder and to measure the disability of the upper extremities which can be related to function. After the intervention, the DASH score in the SEG decreased 6.63 points while in the PNFG, the decrease was by 20.35 points with the differences between both being statistically significant. The improvement obtained, in the case of SEG, was not maintained over time (T0 = 37.74; T1 = 31.11; T2 = 33.89). In contrast, the PNFG result was maintained at the follow-up (T0 = 34.76; T1 = 14.41; T2 = 11.71). The higher the DASH score, the greater the degree of disability. Our results are in line with those obtained by Hagert et al.
      • Hagert E.
      Proprioception of the wrist joint: a review of current concepts and possible implications on the rehabilitation of the wrist.
      and Cantero Téllez et al.,
      • Cantero-Téllez R
      • Medina Porqueres I.
      Practical exercises for thumb proprioception.
      and they support the conclusion that proprioceptive exercises promote motor coordination, making gripping and pinching movements more efficient, which improves the functionality of the hand. The work carried out by Franchignoni et al.
      • Franchignoni F
      • Vercelli S
      • Giordano A
      • Sartorio F
      • Bravini E
      • Ferriero G.
      Minimal clinically important difference of the disabilities of the arm, shoulder and hand outcome measure (DASH) and its shortened version (QuickDASH).
      determined that the lower limit of the minimum clinically important difference (MCID) for the DASH is set at 10.83 points, while the upper limit at 15 points. Taking this data into account and comparing it with our results, only PNFG achieves this MCID. The limitations in daily life activities have been identified as the main factor that reduces the quality of life of patients with CMC OA.
      • Kjeken I
      • Dagfinrud H
      • Slatkowsky-Christensen B
      • et al.
      Activity limitations and participation restrictions in women with hand osteoarthritis: patients’ descriptions and associations between dimensions of functioning.
      ,
      • Kwok WY
      • Vliet Vlieland TPM
      • Rosendaal FR
      • Huizinga TWJ
      • Kloppenburg M
      Limitations in daily activities are the major determinant of reduced health-related quality of life in patients with hand osteoarthritis.
      Numerous papers have argued that proprioception is crucial for the development of everyday manual tasks such as fastening buttons, writing, and picking up small objects.
      • Kjeken I
      • Dagfinrud H
      • Slatkowsky-Christensen B
      • et al.
      Activity limitations and participation restrictions in women with hand osteoarthritis: patients’ descriptions and associations between dimensions of functioning.
      ,
      • Cantero-Téllez R
      • Medina Porqueres I.
      Practical exercises for thumb proprioception.
      ,
      • Yahya A
      • von Behren T
      • Levine S
      • dos Santos M.
      Pinch aperture proprioception: reliability and feasibility study.
      • Roos EM
      • Herzog W
      • Block JA
      • Bennell KL.
      Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis.
      • Hagert E.
      Proprioception of the wrist joint: a review of current concepts and possible implications on the rehabilitation of the wrist.
      Proprioception alterations in arthritic pathologies cause an alteration in the distribution of loads at the joint, affecting the integrity of the cartilage. In turn, these changes cause greater pain and a loss of strength which results in a limitation of functional capacity.
      • Roos EM
      • Herzog W
      • Block JA
      • Bennell KL.
      Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis.
      Pain is one of the main symptoms in women with CMC OA. Our results show that following the intervention, the perceived pain in SEG was reduced by 13.12% (0.69 points), while this reduction was 57.02% (3.37 points) for PNFG, with this difference being statistically significant. It is estimated that in patients with chronic pain, a reduction of approximately 2points or a reduction of approximately 30% represents a clinically important difference.
      • Farrar J
      • Young James P
      • LaMoreaux L
      • Werth J
      • Poole M
      Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale.
      This reduction only occurred in the PNFG. In the follow-up evaluation (T2) in the SEG, the perceived pain increased 0.37 points compared to the post-treatment evaluation (T1). This is unlike the PNFG in which the pain perceived in T2 decreased by 0.17 points. Recent research
      • Clauw DJ
      • Hassett AL
      The role of centralised pain in osteoarthritis.
      maintains that the concept of central sensitization may be the cause of the chronicity and recurrence of pain in thumb osteoarthritis. Furthermore, in the case of women, it is necessary to add that the changes related to the period of transition to menopause can play a fundamental role in the experience of pain. Fluctuations in oestrogen levels, along with those of other reproductive hormones during perimenopause and post-menopause, have an impact on pain modulation and sensitivity.
      • Ma B
      • Yu L
      • Fan J
      • et al.
      Estrogen modulation of peripheral pain signal transduction: involvement of P2X3 receptors.
      These findings raise the possibility that women during menopause may be more vulnerable to pain.
      • Gibson CJ
      • Li Y
      • Bertenthal D
      • Huang AJ
      • Seal KH.
      Menopause symptoms and chronic pain in a national sample of midlife women veterans.
      Exercise can act as a painful conditioning stimulus, thus activating the descending inhibitory pathways, resulting in systemic hypoalgesia.
      • Lemley KJ
      • Drewek B
      • Hunter SK
      Hoeger Bement MK. Pain relief after isometric exercise is not task-dependent in older men and women.
      ,
      • Kosek E
      • Lundberg L
      Segmental and plurisegmental modulation of pressure pain thresholds during static muscle contractions in healthy individuals.
      Acute isometric exercise has been shown to reduce the facilitating mechanisms of central pain (ie the temporal sum of pain).
      • Vaegter HB
      • Handberg G
      • Graven-Nielsen T
      Isometric exercises reduce temporal summation of pressure pain in humans.
      Our results confirm this idea, although on the other hand, they also imply that if strength training is combined with proprioceptive muscle facilitation exercises, the improvement is significantly greater.
      We used the Kapandji test to evaluate the impact of interventions on thumb mobility. The immediate effects of the interventions confirmed an improvement in mobility for both intervention groups. SEG mobility improved by 17.22% while the PNFG improvement was 29.27%, with the difference between both groups being statistically significant. Importantly, only PNFG maintained the effects in the follow-up (T2). There is increasing evidence that oestrogens play a relevant role in maintaining the homeostasis of joint tissues and, therefore, of the joint itself.
      • Roman-Blas JA
      • Castañeda S
      • Largo R
      • Herrero-Beaumont G.
      Osteoarthritis associated with estrogen deficiency.
      ,
      • Martín-Millán M
      • Castañeda S
      Estrogens, osteoarthritis and inflammation.
      Oestrogen deficiency has a great influence on bone formation, the physiological metabolism of bone cells, and the production of inflammatory-related factors associated with chondrocytes.

      Zhang E, Zhang H, Liu F, et al. Estrogen exerts anti-inflammatory effects by inhibiting NF-κB pathway through binding with estrogen receptor β on synovicytes of osteoarthritis. 2016;32(12):1605-1609.

      The sum of these factors causes alterations in the joint cartilage, limiting mobility and consequently the quality of life of women. This is why interventions are needed to alleviate these effects.
      In terms of the strength variables, the SEG showed an improvement in grip of 1.08 kg, while for the palmar it was 0.56 kg, 0.40kg for the tip pinch, and for the key pinch, it was 1.97 kg. In the case of the PNFG, the improvements were 5.19kg, 1.72kg, 1.97kg, and 1.76 respectively. In the work of Villafaine et al.,
      • Villafañe JH
      • Valdes K
      • Bertozzi L
      • Negrini S
      Minimal clinically important difference of grip and pinch strength in women with thumb carpometacarpal osteoarthritis when compared to healthy subjects.
      it has been found that to detect important changes in subjects with CMC OA, there must be an improvement of 0.84 to 1.12 kg for grip, 0.23 to 0.33 for tip, and 0.30 to 0.35 kg for the tripod or palmar pinch. Although minimal clinically important differences are observed in both groups, the improvements are statistically better in the PNFG and they are also maintained in the follow-up. There is evidence confirming that the hormonal changes during menopause have an effect on the decrease in lean mass.
      • Greendale GA
      • Sternfeld B
      • Huang M
      • et al.
      Changes in body composition and weight during the menopause transition.
      • Ho SC
      • Wu S
      • Chan SG
      • Sham A.
      Menopausal transition and changes of body composition: a prospective study in Chinese perimenopausal women.
      • Sipilä S
      • Törmäkangas T
      • Sillanpää E
      • et al.
      Muscle and bone mass in middle-aged women: role of menopausal status and physical activity.
      The study by Steultjens et al.
      • Steultjens MP
      • Dekker J
      • van Baar ME
      • Oostendorp RA
      • Bijlsma JW.
      Muscle strength, pain and disability in patients with osteoarthritis.
      confirms that a decrease in muscle strength can be considered a risk factor that causes pain and disability in osteoarthritis processes. This is because, in the performance of functional daily life tasks, a person needs to be able to generate grip forces between 20 - 25 Kg.
      • Lee S-C
      • Wu L-C
      • Chiang S-L
      • et al.
      Validating the capability for measuring age-related changes in grip-force strength using a digital hand-held dynamometer in healthy young and elderly adults.
      The available literature confirms that exercise programmes are a strategy for improving strength in people with hand osteoarthritis.
      • Østerås N
      • Hagen KB
      • Grotle M
      • Sand-Svartrud A-L
      • Mowinckel P
      • Kjeken I.
      Limited effects of exercises in people with hand osteoarthritis: results from a randomized controlled trial.
      • Hennig T
      • Hæhre L
      • Hornburg VT
      • Mowinckel P
      • Norli ES
      • Kjeken I.
      Effect of home-based hand exercises in women with hand osteoarthritis: a randomised controlled trial.
      • Lourenzi FM
      • Jones A
      • Pereira DF
      • Santos JHCAD
      • Furtado RNV
      • Natour J.
      Effectiveness of an overall progressive resistance strength program for improving the functional capacity of patients with rheumatoid arthritis: a randomized controlled trial.
      Specifically, Osteras et al.
      • Østerås N
      • Kjeken I
      • Smedslund G
      • et al.
      Exercise for hand osteoarthritis.
      reported that after a strength programme, the participants showed improved hand function. Our results confirm this hypothesis as both programmes improved the level of functionality in post-menopausal women with CMC OA. To our knowledge, this is the first work that uses proprioceptive neuromuscular facilitation techniques combined with strength training for post-menopausal women.

      Limitations

      The main limitation in relation to the generalizability of the current study is the small sample size, although the number of recruited participants was sufficient in accordance with an a priori power analysis. Another limitation was that the VAS was used to assess pain. It would have been interesting to use the pressure pain threshold. Furthermore, the study design did not include a control group or a group that performed only proprioceptive muscle facilitation exercises while not including a follow-up measurement at 3 and 6 months to analyze the long-term effects of the treatment. Future studies in larger populations and including follow-up measurements should be performed to confirm our findings and the duration of the beneficial effects.

      Conclusions

      The results obtained confirm the hypothesis proposed by this study. The combination of proprioceptive muscle facilitation exercises and strength training is more effective for reducing disability and pain, as well as for the improvement of mobility and strength in post-menopausal women with thumb CMC OA than a programme based solely on strength training.

      Author Contributions

      CCA, CI and JMT, made a substantial contribution to the concept of the work, SPA, JJC and SCA on the writing of the manuscript. CCA performed the recruitment of participants and data collection. All authors revised the manuscript critically for important intellectual content, read and approved the final version to be published.

      References

        • Schopflocher D
        • Taenzer P
        • Jovey R.
        The prevalence of chronic pain in Canada.
        Pain Res Manag. 2011; 16: 445-450
        • Lee HJ
        • Paik N-J
        • Lim J-Y
        • Kim KW
        • Gong HS.
        The impact of digit-related radiographic osteoarthritis of the hand on grip-strength and upper extremity disability.
        Clin Orthop. 2012; 470: 2202-2208
        • Murphy L
        • Helmick CG.
        The impact of osteoarthritis in the United States: a population-health perspective: a population-based review of the fourth most common cause of hospitalization in U.S. adults.
        Orthop Nurs. 2012; 31: 85-91
        • Carmona L
        • Episer G de E
        • Laffon A
        • Ballina J
        • Gabriel R.
        Proyecto EPISER 2000: prevalencia de enfermedades reumáticas en la población española. metodología, resultados del reclutamiento y características de la población.
        Rev Esp Reumatol Órgano Of Soc Esp Reumatol. 2001; 28: 18-25
        • Sodha S
        • Ring D
        • Zurakowski D
        • Jupiter JB.
        Prevalence of osteoarthrosis of the trapeziometacarpal joint.
        J Bone Joint Surg Am. 2005; 87: 2614-2618
        • Haara MM
        • Heliövaara M
        • Kröger H
        • et al.
        Osteoarthritis in the carpometacarpal joint of the thumb prevalence and associations with disability and mortality.
        J Bone Joint Surg Am. 2004; 86: 1452-1457
        • Pai S
        • Talwalkar S
        • Hayton M.
        Presentation and management of arthritis affecting the trapezio-metacarpal joint.
        Acta Orthop Belg. 2006; 72: 3-10
        • Wilder FV
        • Barrett JP
        • Farina EJ.
        Joint-specific prevalence of osteoarthritis of the hand.
        Osteoarthritis Cartilage. 2006; 14: 953-957
        • Kjeken I
        • Dagfinrud H
        • Slatkowsky-Christensen B
        • et al.
        Activity limitations and participation restrictions in women with hand osteoarthritis: patients’ descriptions and associations between dimensions of functioning.
        Ann Rheum Dis. 2005; 64: 1633-1638
        • Faour-Martín O
        • Martín-Ferrero MÁ
        • Valverde-García JA
        • Vega-Castrillo A
        • De La
        • Red-Gallego MÁ.
        Rhizarthrosis fourth grade of eaton with hyperextension of the metacarpophalangeal joint.
        Int J Surg Case Rep. 2013; 4: 929-932
        • Bertozzi L
        • Valdes K
        • Vanti C
        • Negrini S
        • Pillastrini P
        • Villafañe JH.
        Investigation of the effect of conservative interventions in thumb carpometacarpal osteoarthritis: systematic review and meta-analysis.
        Disabil Rehabil. 2015; 37: 2025-2043
        • Berggren M
        • Joost-Davidsson A
        • Lindstrand J
        • Nylander G
        • Povlsen B.
        Reduction in the need for operation after conservative treatment of osteoarthritis of the first carpometacarpal joint: a seven-year prospective study.
        Scand J Plast Reconstr Surg Hand Surg. 2001; 35: 415-417
        • O'Brien VH
        • Giveans MR.
        Effects of a dynamic stability approach in conservative intervention of the carpometacarpal joint of the thumb: a retrospective study.
        J Hand Ther Off J Am Soc Hand Ther. 2013; 26: 44-51
        • Kjeken I
        • Smedslund G
        • Moe RH
        • Slatkowsky-Christensen B
        • Uhlig T
        • Hagen KB.
        Systematic review of design and effects of splints and exercise programs in hand osteoarthritis.
        Arthritis Care Res. 2011; 63: 834-848
        • Villafañe JH
        • Cleland JA
        Fernández-de-Las-Peñas C. The effectiveness of a manual therapy and exercise protocol in patients with thumb carpometacarpal osteoarthritis: a randomized controlled trial.
        J Orthop Sports Phys Ther. 2013; 43: 204-213
        • Kamaruzaman H
        • Kinghorn P
        • Oppong R.
        Costeffectiveness of surgical interventions for the management of osteoarthritis: a systematic review of the literature.
        BMC Musculoskelet Disord. 2017; 18: 183
        • Wouters RM
        • Vranceanu A-M
        • Slijper HP
        • et al.
        Patients with thumb-base osteoarthritis scheduled for surgery have more symptoms, worse psychological profile, and higher expectations than nonsurgical counterparts: a large cohort analysis.
        Clin Orthop. 2019; 477: 2735-2746
        • Spaans AJ
        • van Minnen LP
        • Kon M
        • Schuurman AH
        • Schreuders ART
        • Vermeulen GM.
        Conservative treatment of thumb base osteoarthritis: a systematic review.
        J Hand Surg. 2015; 40: 16-21.e1-6
        • Kloppenburg M
        • Kroon FP
        • Blanco FJ
        • et al.
        update of the EULAR recommendations for the management of hand osteoarthritis.
        Ann Rheum Dis. 2019; 78: 16-24
        • Østerås N
        • Kjeken I
        • Smedslund G
        • et al.
        Exercise for hand osteoarthritis: a cochrane systematic Review.
        J Rheumatol. 2017; 44: 1850-1858
        • Villafañe JH
        • Valdes K
        • Pedersini P
        • Berjano P.
        Thumb carpometacarpal osteoarthritis: a musculoskeletal physiotherapy perspective.
        J Bodyw Mov Ther. 2019; 23: 908-912
        • Kroon FP
        • Carmona L
        • Schoones JW
        • Kloppenburg M.
        Efficacy and safety of non-pharmacological, pharmacological and surgical treatment for hand osteoarthritis: a systematic literature review informing the 2018 update of the EULAR recommendations for the management of hand osteoarthritis.
        RMD Open. 2018; 4e000734
        • Zhang W
        • Doherty M
        • Leeb BF
        • et al.
        EULAR evidence based recommendations for the management of hand osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).
        Ann Rheum Dis. 2007; 66: 377-388
        • Hochberg MC
        • Altman RD
        • April KT
        • et al.
        American college of rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee.
        Arthritis Care Res. 2012; 64: 465-474
        • Moe RH
        • Kjeken I
        • Uhlig T
        • Hagen KB.
        There is inadequate evidence to determine the effectiveness of nonpharmacological and nonsurgical interventions for hand osteoarthritis: an overview of high-quality systematic reviews.
        Phys Ther. 2009; 89: 1363-1370
        • Smedes F
        • Heidmann M
        • Schäfer C
        • Fischer N
        • Stępień A
        The proprioceptive neuromuscular facilitation-concept; the state of the evidence, a narrative review.
        Physical Therapy Reviews. 2016; 21: 17-31
        • Shimura K
        • Kasai T.
        Effects of proprioceptive neuromuscular facilitation on the initiation of voluntary movement and motor evoked potentials in upper limb muscles.
        Hum Mov Sci. 2002; 21: 101-113
        • Song Q
        • Shen P
        • Mao M
        • Sun W
        • Zhang C
        • Li L.
        Proprioceptive neuromuscular facilitation improves pain and descending mechanics among elderly with knee osteoarthritis.
        Scand J Med Sci Sports. 2020; 30: 1655-1663
        • Birinci T
        • Razak Ozdincler A
        • Altun S
        • Kural C
        A structured exercise programme combined with proprioceptive neuromuscular facilitation stretching or static stretching in posttraumatic stiffness of the elbow: a randomized controlled trial.
        Clin Rehabil. 2019; 33: 241-252
        • Balcı NC
        • Yuruk ZO
        • Zeybek A
        • Gulsen M
        • Tekindal MA.
        Acute effect of scapular proprioceptive neuromuscular facilitation (PNF) techniques and classic exercises in adhesive capsulitis: a randomized controlled trial.
        J Phys Ther Sci. 2016; 28: 1219-1227
        • Çelik MS
        • Sönmezer E
        • Acar M.
        Effectiveness of proprioceptive neuromuscular facilitation and myofascial release techniques in patients with subacromial impingement syndrome.
        Somatosens Mot Res. 2022; 7: 1-9
        • Kennedy CD
        • Manske MC
        • Huang JI.
        Classifications in brief: the eaton-littler classification of thumb carpometacarpal joint arthrosis.
        Clin Orthop. 2016; 474: 2729-2733
        • MacDermid J.
        Clinical Assessment Recommendations.
        3rd ed. American Society of Hand Therapy, Muont Laurel, NJ2015
        • Hervás MT
        • Navarro Collado MJ
        • Peiró S
        • Rodrigo Pérez JL
        • López Matéu P
        • Martínez Tello I.
        Versión española del cuestionario DASH. Adaptación transcultural, fiabilidad, validez y sensibilidad a los cambios [Spanish version of the DASH questionnaire. Cross-cultural adaptation, reliability, validity and responsiveness].
        Med Clin (Barc). 2006; 127: 441-447
        • Raven EE
        • Haverkamp D
        • Sierevelt IN
        • et al.
        Construct validity and reliability of the disability of arm, shoulder and hand questionnaire for upper extremity complaints in rheumatoid arthritis.
        J Rheumatol. 2008; 35: 2334-2338https://doi.org/10.3899/jrheum.080067
        • Haefeli M
        • Elfering A.
        Pain assessment.
        Eur Spine J. 2006; 15: S17-S24
        • Kapandji A.
        Clinical test of apposition and counter-apposition of the thumb.
        Ann Chir Main Organe Off Soc Chir Main. 1986; 5: 67-73
        • Mathiowetz V
        • Kashman N
        • Volland G
        • Weber K
        • Dowe M
        • Rogers S.
        Grip and pinch strength: normative data for adults.
        Arch Phys Med Rehabil. 1985; 66: 69-74
        • Hagert E.
        Proprioception of the wrist joint: a review of current concepts and possible implications on the rehabilitation of the wrist.
        J Hand Ther Off J Am Soc Hand Ther. 2010; 23: 2-17
        • Cantero-Téllez R
        • Medina Porqueres I.
        Practical exercises for thumb proprioception.
        J Hand Ther. 2021.; 34: 488-492
        • Franchignoni F
        • Vercelli S
        • Giordano A
        • Sartorio F
        • Bravini E
        • Ferriero G.
        Minimal clinically important difference of the disabilities of the arm, shoulder and hand outcome measure (DASH) and its shortened version (QuickDASH).
        J Orthop Sports Phys Ther. 2014; 44: 30-39
        • Kwok WY
        • Vliet Vlieland TPM
        • Rosendaal FR
        • Huizinga TWJ
        • Kloppenburg M
        Limitations in daily activities are the major determinant of reduced health-related quality of life in patients with hand osteoarthritis.
        Ann Rheum Dis. 2011; 70: 334-336
        • Yahya A
        • von Behren T
        • Levine S
        • dos Santos M.
        Pinch aperture proprioception: reliability and feasibility study.
        J Phys Ther Sci. 2018; 30: 734-740
        • Roos EM
        • Herzog W
        • Block JA
        • Bennell KL.
        Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis.
        Nat Rev Rheumatol. 2011; 7: 57-63
        • Hagert E.
        Proprioception of the wrist joint: a review of current concepts and possible implications on the rehabilitation of the wrist.
        J Hand Ther Off J Am Soc Hand Ther. 2010; 23: 2-17
        • Farrar J
        • Young James P
        • LaMoreaux L
        • Werth J
        • Poole M
        Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale.
        Pain. 2001; 94: 149-158https://doi.org/10.1016/S0304-3959(01)00349-9
        • Clauw DJ
        • Hassett AL
        The role of centralised pain in osteoarthritis.
        Clin Exp Rheumatol. 2017; 35: 79-84
        • Ma B
        • Yu L
        • Fan J
        • et al.
        Estrogen modulation of peripheral pain signal transduction: involvement of P2X3 receptors.
        Purinergic Signal. 2011; 7: 73-83
        • Gibson CJ
        • Li Y
        • Bertenthal D
        • Huang AJ
        • Seal KH.
        Menopause symptoms and chronic pain in a national sample of midlife women veterans.
        Menopause N Y N. 2019; 26: 708-713
        • Lemley KJ
        • Drewek B
        • Hunter SK
        Hoeger Bement MK. Pain relief after isometric exercise is not task-dependent in older men and women.
        Med Sci Sports Exerc. 2014; 46: 185-191
        • Kosek E
        • Lundberg L
        Segmental and plurisegmental modulation of pressure pain thresholds during static muscle contractions in healthy individuals.
        Eur J Pain Lond Engl. 2003; 7: 251-258
        • Vaegter HB
        • Handberg G
        • Graven-Nielsen T
        Isometric exercises reduce temporal summation of pressure pain in humans.
        Eur J Pain Lond Engl. 2015; 19: 973-983
        • Roman-Blas JA
        • Castañeda S
        • Largo R
        • Herrero-Beaumont G.
        Osteoarthritis associated with estrogen deficiency.
        Arthritis Res Ther. 2009; 11: 241
        • Martín-Millán M
        • Castañeda S
        Estrogens, osteoarthritis and inflammation.
        Joint Bone Spine julio de. 2013; 80: 368-373
      1. Zhang E, Zhang H, Liu F, et al. Estrogen exerts anti-inflammatory effects by inhibiting NF-κB pathway through binding with estrogen receptor β on synovicytes of osteoarthritis. 2016;32(12):1605-1609.

        • Villafañe JH
        • Valdes K
        • Bertozzi L
        • Negrini S
        Minimal clinically important difference of grip and pinch strength in women with thumb carpometacarpal osteoarthritis when compared to healthy subjects.
        Rehabil Nurs. 2017; 42: 139-145
        • Greendale GA
        • Sternfeld B
        • Huang M
        • et al.
        Changes in body composition and weight during the menopause transition.
        JCI Insight. 2019; 7124865
        • Ho SC
        • Wu S
        • Chan SG
        • Sham A.
        Menopausal transition and changes of body composition: a prospective study in Chinese perimenopausal women.
        Int J Obes. 2010; 34: 1265-1274
        • Sipilä S
        • Törmäkangas T
        • Sillanpää E
        • et al.
        Muscle and bone mass in middle-aged women: role of menopausal status and physical activity.
        J Cachexia Sarcopenia Muscle. 2020; 11: 698-709
        • Steultjens MP
        • Dekker J
        • van Baar ME
        • Oostendorp RA
        • Bijlsma JW.
        Muscle strength, pain and disability in patients with osteoarthritis.
        Clin Rehabil. 2001; 15: 331-341
        • Lee S-C
        • Wu L-C
        • Chiang S-L
        • et al.
        Validating the capability for measuring age-related changes in grip-force strength using a digital hand-held dynamometer in healthy young and elderly adults.
        Biomed Res Int. 2020; 20206936879
        • Østerås N
        • Hagen KB
        • Grotle M
        • Sand-Svartrud A-L
        • Mowinckel P
        • Kjeken I.
        Limited effects of exercises in people with hand osteoarthritis: results from a randomized controlled trial.
        Osteoarthritis Cartilage. 2014; 22: 1224-1233
        • Hennig T
        • Hæhre L
        • Hornburg VT
        • Mowinckel P
        • Norli ES
        • Kjeken I.
        Effect of home-based hand exercises in women with hand osteoarthritis: a randomised controlled trial.
        Ann Rheum Dis. 2015; 74: 1501-1508
        • Lourenzi FM
        • Jones A
        • Pereira DF
        • Santos JHCAD
        • Furtado RNV
        • Natour J.
        Effectiveness of an overall progressive resistance strength program for improving the functional capacity of patients with rheumatoid arthritis: a randomized controlled trial.
        Clin Rehabil. 2017; 31: 1482-1491
        • Østerås N
        • Kjeken I
        • Smedslund G
        • et al.
        Exercise for hand osteoarthritis.
        Cochrane Database Syst Rev. 2017; 1CD010388