The Osteoblast Transcriptome in Developing Zebrafish Reveals Key Roles for Extracellular Matrix Proteins Col10a1a and Fbln1 in Skeletal Development and Homeostasis.

Zebrafish are now widely used to study skeletal development and bone-related diseases. To that end, understanding osteoblast differentiation and function, the expression of essential transcription factors, signaling molecules, and extracellular matrix proteins is crucial. We isolated Sp7-expressing osteoblasts from 4-day-old larvae using a fluorescent reporter. We identified two distinct subpopulations and characterized their specific transcriptome as well as their structural, regulatory, and signaling profile. Based on their differential expression in these subpopulations, we generated mutants for the extracellular matrix protein genes col10a1a and fbln1 to study their functions. The col10a1a-/- mutant larvae display reduced chondrocranium size and decreased bone mineralization, while in adults a reduced vertebral thickness and tissue mineral density, and fusion of the caudal fin vertebrae were observed. In contrast, fbln1-/- mutants showed an increased mineralization of cranial elements and a reduced ceratohyal angle in larvae, while in adults a significantly increased vertebral centra thickness, length, volume, surface area, and tissue mineral density was observed. In addition, absence of the opercle specifically on the right side was observed. Transcriptomic analysis reveals up-regulation of genes involved in collagen biosynthesis and down-regulation of Fgf8 signaling in fbln1-/- mutants. Taken together, our results highlight the importance of bone extracellular matrix protein genes col10a1a and fbln1 in skeletal development and homeostasis.

New ex vivo method to objectively assess insulin spatial subcutaneous dispersion through time during pump basal-rate based administration.

Glycemic variability remains frequent in patients with type 1 diabetes treated with insulin pumps. Heterogeneous spreads of insulin infused by pump in the subcutaneous (SC) tissue are suspected but were barely studied. We propose a new real-time ex-vivo method built by combining high-precision imaging with simultaneous pressure measurements, to obtain a real-time follow-up of insulin subcutaneous propagation. Human skin explants from post-bariatric surgery are imaged in a micro-computed tomography scanner, with optimised parameters to reach one 3D image every 5 min during 3 h of 1UI/h infusion. Pressure inside the tubing is recorded. A new index of dispersion (IoD) is introduced and computed upon the segmented 3D insulin depot per time-step. Infusions were hypodermal in 58.3% among 24 assays, others being intradermal or extradermal. Several minor bubbles and one occlusion were observed. IoD increases with time for all injections. Inter-assay variability is the smallest for hypodermal infusions. Pressure elevations were observed, synchronised with air bubbles arrivals in the tissue. Results encourage the use of this method to compare infusion parameters such as pump model, basal rate, catheter characteristics, infusion site characteristics or patient phenotype.

Effectiveness of topical sodium thiosulfate for ectopic calcifications and ossifications. Results of the CATSS-O study.

INTRODUCTION: Ectopic calcifications (ECs) and heterotopic ossifications (HOs) form in non-mineralized tissues, most often in subcutaneous and muscular areas. Local and systemic complications can cause severe disability. Systemic administration of sodium thiosulfate (STS) gives promising results but is difficult to use in clinical practice. OBJECTIVE: Evaluation of the efficacy and safety of topical STS in ECs and HOs. METHODS: Retrospective analysis of the CATSS-O registry that included patients receiving topical STS 25 % prepared by the pharmacy of Limoges hospital during 2014-2020. The efficacy of STS was assessed by imaging (radiography or CT) after at least 6 months' treatment. RESULTS: Among 126 patients who received STS 25 %, 35 had complete clinical and radiographic data for analysis (28 with ECs and 7 with HOs; 18 children [mean age 8.9 years, range 1.5-16], 17 adults [mean age 52.4 years, range 24-90]). Calcifications or ossifications were due to dermatomyositis (8 children, 6 adults), systemic scleroderma (6 adults) or pseudo-hypoparathyroidism 1A (7 children). They were single (37.1 %) or multiple (62.9 %). Treated regions were in the lower limbs (31.4 %), upper limbs (37.1 %) or both (28.6 %) and the axial region (2.9 %). Topical STS was clinically effective in 9/28 (32.1 %) patients with ECs and 2/7 (28.6 %) children with HOs. Three patients experienced complete disappearance of their calcifications. Response for ECs was better in children than adults (54.5% vs 17.6 %, p = 0.035). Topical STS was well tolerated. CONCLUSION: Local STS seems effective for ossifications, particularly pediatric calcifications or ossifications. Randomized and experimental studies are needed to confirm this observation and to identify the underlying mechanisms.

Economic impact of work disability due to chronic low back pain from the patient perspective.

OBJECTIVES: Low back pain (LBP) is one of the main expenditure items for health systems. Data on the economic impact of LBP are uncommon from the patient perspective. The aim of this study was to estimate the economic impact of work disability related to chronic LBP from the patient perspective. METHODS: We conducted a cross-sectional analysis from patients aged over 17 years suffering from non-specific LBP for at least 3 months. Systematic medical, social and economic assessments were collected: pain duration and intensity; functional disability with the Quebec Back Pain Disability Scale (0-100); quality of life with the Dallas Pain Questionnaire; job category; employment status; duration of work disability due to LBP, and income. Factors associated with loss of income were identified by multivariable logistic regression analysis. RESULTS: We included 244 workers (mean age 43 ± 9 years; 36% women); 199 patients had work disability, including 196 who were on sick leave, 106 due to job injury. Three were unemployed due to layoff for incapacity. The mean loss of income for patients with work disability was 14% [SD 24, range -100 to 70] and was significantly less for patients on sick leave due to job injury than on sick leave not related to job injury (p < 0.0001). On multivariable analysis, the probability of loss of income with LBP was about 50% less for overseers and senior managers than workers or employees (odds ratio 0.48 [95% confidence interval 0.23-0.99]). CONCLUSION: Work disability due to LBP resulted in loss of income in our study. The loss of income depended on the type of social protection and job category. It was reduced for patients on sick leave related to work injury and for overseers and senior managers.

wnt11f2 Zebrafish, an Animal Model for Development and New Insights in Bone Formation.

Wnt signaling is a key regulator of osteoblast differentiation and mineralization in humans and animals, mediated by the canonical Wnt/ß-catenin and noncanonical signaling pathways. Both pathways are crucial in regulating osteoblastogenesis and bone formation. The zebrafish silberblick (slb) carries a mutation in wnt11f2, a gene that contributes to embryonic morphogenesis; however, its role in bone morphology is unknown. wnt11f2 was originally known as wnt11; it was recently reclassified to avoid confusion in comparative genetics and disease modeling. The goal of this review is to summarize the characterization of the wnt11f2 zebrafish mutant and to deliver some new insights concerning its role in skeletal development. In addition to the previously described defects in early development in this mutant as well as craniofacial dysmorphia, we show an increase in tissue mineral density in the heterozygous mutant that points to a possible role of wnt11f2 in high bone mass phenotypes.

A Zebrafish Mutant in the Extracellular Matrix Protein Gene efemp1 as a Model for Spinal Osteoarthritis.

Osteoarthritis is a degenerative articular disease affecting mainly aging animals and people. The extracellular matrix protein Efemp1 was previously shown to have higher turn-over and increased secretion in the blood serum, urine, and subchondral bone of knee joints in osteoarthritic patients. Here, we use the zebrafish as a model system to investigate the function of Efemp1 in vertebrate skeletal development and homeostasis. Using in situ hybridization, we show that the efemp1 gene is expressed in the brain, the pharyngeal arches, and in the chordoblasts surrounding the notochord at 48 hours post-fertilization. We generated an efemp1 mutant line, using the CRISPR/Cas9 method, that produces a severely truncated Efemp1 protein. These mutant larvae presented a medially narrower chondrocranium at 5 days, which normalized later at day 10. At age 1.5 years, µCT analysis revealed an increased tissue mineral density and thickness of the vertebral bodies, as well as a decreased distance between individual vertebrae and ruffled borders of the vertebral centra. This novel defect, which has, to our knowledge, never been described before, suggests that the efemp1 mutant represents the first zebrafish model for spinal osteoarthritis.

New insights into the role of matrix metalloproteinase 3 (MMP3) in bone.

The Matrix Metalloproteinases are important regulators of bone metabolism and can influence bone mass and bone remodeling. We investigate the role of Matrix Metalloproteinase 3 (MMP3) on bone in mice, by using Mmp3 knockout (Mmp3 KO) in the context of estrogen deficiency, and in human, by analyzing the association of promoter polymorphism with bone mineral density in postmenopausal women and with MMP3 expression. We presented evidence in this paper that Mmp3 KO significantly increases trabecular bone mass and trabecular number and does not affect cortical bone thickness. We also found that Mmp3 KO protects from the deleterious effects of ovariectomy on bone mineral density in mice by preventing deterioration of bone microarchitecture. The effect of Mmp3 KO does not involve bone formation parameters but instead acts by inhibition of bone resorption, leading to a reduced bone loss associated to ovariectomy. By studying a human cohort, we found that a polymorphism located in the promoter of the human MMP3 gene is associated with bone mineral density in postmenopausal women and found that MMP3 rs632478 promoter variants are associated with change in promoter activity in transfection experiments. In conclusion MMP3, although weakly expressed in bone cells, could be one of the important regulators of sex hormone action in bone and whose activity could be targeted for therapeutic applications such as in Osteoporosis.

Value of a clinical test of sub-acromial impingement to predict response to physiotherapy with dynamic humeral centering: A preliminary study.

BACKGROUND: Dynamic humeral centering (DHC) is a physiotherapy modality that aims to prevent sub-acromial impingement of rotator cuff tendons. We recently developed a new clinical manoeuver - the Viggo-Cochin test - to enhance the ability of the Neer test to detect sub-acromial impingement. Here we hypothesised whether the DHC effect may differ between individuals with positive and negative Viggo-Cochin test results. OBJECTIVE: To assess the association between DHC and Viggo-Cochin test results. METHODS: Individuals with shoulder pain due to sub-acromial impingement underwent the Neer and Viggo-Cochin tests at baseline. They were assessed before and after DHC by the Shoulder Pain and Disability Index (SPADI). A positive response to DHC was defined as a 20% reduction in the SPADI. RESULTS: We included 50 individuals (53 shoulders). The response to DHC did not differ by Neer test result at baseline: OR 0.73 [95% CI 0.22-2.38] (p= 0.601). By contrast, the response to DHC was 5-fold higher with a positive than negative Viggo-Cochin test result: OR 5.11 [95% CI 1.47-17.78] (p= 0.010). CONCLUSIONS: We found a higher clinical response to DHC with a positive than negative Viggo-Cochin test result at baseline in individuals with shoulder pain due to rotator cuff disease.

Calcium pyrophosphate crystal deposition in a cohort of 57 patients with Gitelman syndrome.

OBJECTIVE: Gitelman syndrome (GS) is the most frequent salt-wasting genetic tubulopathy and a source of hypokalaemia and hypomagnesemia. Chondrocalcinosis (CC) is a frequent feature of GS. The aim of our study was to determine the prevalence, distribution patterns, clinical phenotypes and risk factors for CC in GS. METHODS: This prospective study of a cohort of 57 patients with GS included a systematic screening for CC by peripheral joint radiography, cervical spine CT and joint US. The prevalence of cervical C1-C2 CC by CT was compared between 33 GS patients and sex- and age-matched controls. Clinical and biochemical features were analysed to identify factors associated with CC. RESULTS: Mean (s.d.) age of patients was 46.5 (12.4) years, 66.7% were women and 93.0% carried SLC12A3 mutations. Mean serum magnesium level was 0.60 (0.30) mmol/l. CC was observed in 79% of patients, with the highest prevalence at the cervical spine (81.8%) followed by the knee (52.6%), wrist (50.9%), ankle (38.6%), TM joint (36.4%), shoulder (33.3%), hip (22.8%), elbow (14.0%) and sclerochoroid (12.1%). Prevalence of CC at the C1-C2 level was higher in the GS cohort than control group (72.7% vs 9.1%) (adjusted odds ratio 21.0, 95% CI 2.8, 156.1, P = 0.003). Independent factors associated with CC were low serum magnesium level and age. CONCLUSION: GS was associated with widespread CC, favoured by aging and hypomagnesemia. The C1-C2 level was the most affected site. Follow-up of this unique cohort will help understanding the clinical consequences of CC, especially the precise characterization of pyrophosphate arthropathy.

Inadequate response to treatment reveals persistent osteoclast bone resorption in osteoporotic patients.

Several drugs are able to reduce fracture risk in osteoporotic patients. Incident fractures occur despite good adherence to treatment. Inadequate response has been found related to high serum bone biomarkers of bone turnover. We here aimed to analyze bone microarchitecture and cellular profiles of inadequate responders. We retrospectively analyzed bone biopsies from patients with major fractures despite long-term treatment (inadequate responder [IR] n = 31) in comparison to patients with untreated osteoporosis (U-OP, n = 31) and controls without osteoporosis (Ctrl, n = 16). Bone samples were analyzed by histomorphometry and micro-computed tomography. Clinical and bone turnover markers and bone mineral density were assessed. As compared with U-OP patients, IRs were older (mean age 69.7 ± 8.8 vs 63.3 ± 9.3 years, p = 0.007) and had lower mean hip bone mineral density (0.685 ± 0.116 vs 0.786 ± 0.093 g/cm2), p = 0.019 and T-score (-2.3 ± 0.769 vs -1.6 ± 0.900, p = 0.032). BV/TV was lower for IRs than U-OP patients and Ctrls (13.9 ± 3.8% vs 15.2 ± 5.1 and 17.6 ± 5.2%, p = 0.044) as was trabecular thickness (145.6 ± 23.1 vs 160.5 ± 22.7 and 153.7 ± 21.4 µm, p = 0.033). Mean structure model index was lower for IRs than U-OP patients (1.9 ± 0.806 vs 2.4 ± 0.687, p = 0.042) and osteoclast number was higher for IRs than U-OP patients and Ctrls (0.721 ± 0.611 vs 0.394 ± 0.393 and 0.199 ± 0.071 mm-2, p < 0.001). The mean Obl.S/BS was lower for IRs than U-OP patients and Ctrls (1.2 ± 1.3 vs 1.9 ± 1.4 and 3.0 ± 0.638 mm-2, p < 0.0001), and the mean number of labelled surfaces was lower for IRs than U-OP patients (51.6% vs 87%, p = 0.002). Cortical parameters did not significantly differ. We show an imbalance of bone remodeling in favor of bone resorption in IRs. The persistence of high bone resorption suggests insufficient inhibition of bone resorption that could explain the incident fractures with anti-osteoporotic drug use. Adaptation to treatment should be considered to inhibit bone resorption and prevent further fractures.

Longitudinal Bone Loss Occurs at the Radius in CKD.

INTRODUCTION: Chronic kidney disease (CKD) exposes to an increased incidence of fragility fractures. International guidelines recommend performing bone mineral density (BMD) if the results will impact treatment decisions. It remains unknown where bone loss occurs and what would preclude the longitudinal loss in patients with CKD. Here, we aimed to investigate factors influencing BMD and to analyze the longitudinal BMD changes. METHODS: In the NephroTest cohort, we measured BMD at the femoral neck, total hip, lumbar spine, and proximal radius, together with circulating biomarkers and standardized measured glomerular filtration rate (mGFR) by 51Cr-EDTA in a subset of patients with CKD stage 1 to 5 followed during 4.3 ± 2.0 years. A linear mixed model explored the longitudinal bone loss and the relationship of associated factors with BMD changes. A total of 858 patients (mean age 58.9 ± 15.2 years) had at least 1 and 477 had at least 2 BMD measures. RESULTS: At baseline, cross-sectional analysis showed a significantly lower BMD at femoral neck and total hip and a significant higher serum parathyroid hormone (PTH) along with CKD stages. Baseline age, gender, tobacco, low body mass index (BMI), and high PTH levels were significantly associated with low BMD. Longitudinal analysis during the mean 4.3 years revealed a significant bone loss at the radius only. BMD changes at the femoral neck were associated with BMI, but not CKD stages or basal PTH levels. CONCLUSIONS: CKD is associated with low BMD and high PTH in the cross-sectional analysis. Longitudinal bone loss occurred at the proximal radius after 4.3 years.

Compromised Volumetric Bone Density and Microarchitecture in Men With Congenital Hypogonadotropic Hypogonadism.

CONTEXT: Men with congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) have both low circulating testosterone and estradiol levels. Whether bone structure is affected remains unknown. OBJECTIVE: To characterize bone geometry, volumetric density and microarchitecture in CHH/KS. METHODS: This cross-sectional study, conducted at a single French tertiary academic medical center, included 51 genotyped CHH/KS patients and 40 healthy volunteers. Among CHH/KS men, 98% had received testosterone and/or combined gonadotropins. High-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy x-ray absorptiometry (DXA), and measurement of serum bone markers were used to determine volumetric bone mineral density (vBMD) and cortical and trabecular microarchitecture. RESULTS: CHH and controls did not differ for age, body mass index, and levels of vitamin D and PTH. Despite long-term hormonal treatment (10.8 ± 6.8 years), DXA showed lower areal bone mineral density (aBMD) in CHH/KS at lumbar spine, total hip, femoral neck, and distal radius. Consistent with persistently higher serum bone markers, HR-pQCT revealed lower cortical and trabecular vBMD as well as cortical thickness at the tibia and the radius. CHH/KS men had altered trabecular microarchitecture with a predominant decrease of trabecular thickness. Moreover, CHH/KS men exhibited lower cortical bone area, whereas total and trabecular areas were higher only at the tibia. Earlier treatment onset (before age 19 years) conferred a significant advantage for trabecular bone volume/tissue volume and trabecular vBMD at the tibia. CONCLUSION: Both vBMD and bone microarchitecture remain impaired in CHH/KS men despite long-term hormonal treatment. Treatment initiation during adolescence is associated with enhanced trabecular outcomes, highlighting the importance of early diagnosis.

Calcium Pyrophosphate Dihydrate Crystal Deposition in Gouty Tophi.

OBJECTIVE: The coexistence of calcium pyrophosphate dihydrate (CPPD) and monosodium urate monohydrate crystals in gouty tophi has rarely been reported. We undertook this study to investigate CPPD crystal deposits in a series of surgically removed gouty tophi and to identify factors associated with these deposits. METHODS: Twenty-five tophi from 22 gout patients were analyzed using polarized light microscopy, field emission scanning electron microscopy (FESEM), and µ Fourier transform infrared (µFTIR) spectroscopy. RESULTS: Tophi consisted of multiple lobules separated by fibrous septa and surrounded by a foreign-body giant cell reaction. CPPD crystal aggregates were identified in 9 of 25 tophi from 6 patients. CPPD crystals were dispersed or highly compacted, localized at the edge or inside the tophus lobules, with some lobules completely filled with crystals. Both monoclinic and triclinic CPPD crystal phases were identified using FESEM and µFTIR. Compared to patients without CPPD, those with CPPD-containing tophi were older (mean 60.5 years versus 47.2 years; P = 0.009), and had longer-term gout duration (mean 17.0 years versus mean 9.0 years; P < 0.05) and tophi duration (mean 10.0 years versus mean 4.6 years; P < 0.01). None of the patients had radiographic chondrocalcinosis of the knee or wrist. CONCLUSION: CPPD crystal formation seems to be a late and frequent event of tophus maturation, occurring more frequently with aging, and could contribute to the speed of tophus dissolution and the apparent persistence of tophus sometimes observed even after effective, long-lasting urate-lowering therapy.

Cortical Bone Microarchitecture in Dialysis Patients.

BACKGROUND: The incidence of skeletal fractures is high in dialysis patients. Current available tools are insufficient to predict bone fragility. We analyzed the microarchitecture in patients on dialysis therapy using bone biopsies and peripheral microcomputed tomography. METHODS: We analyzed 12 trans-iliac bone biopsies of patients with recent fractures. Bone microarchitecture was assessed in the bone cores by histology (2D-), microcomputed tomography (3D-µCT), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia. RESULTS: Trabecular bone volume/tissue volume was similar in 2D histology and 3D-µCT (p = 0.40), while lower in HR-pQCT (p < 0.01). There was no correlation in trabecular microarchitectural indices between 2-histology and 3D-µCT, or HR-pQCT. The 3D-µCT cortical thickness (Ct.Th) were positively correlated with 2D (p < 0.05), but with HR-pQCT (p = 0.33). Ct.Th was lower in patients with ≥2 vertebral fractures than with one fracture. CONCLUSIONS: 3D-µCT is a reliable method for the measurement of cortical bone in bone biopsies. Prospective studies are awaited to address its value in discriminating fracture risk.

Disruption of Bone Zinc Metabolism during Postnatal Development of Rats after Early Life Exposure to Cadmium.

This current study was conducted to investigate whether bone tissue impairment induced by early life exposure to cadmium (Cd) during postnatal development could result from disruption to zinc (Zn) metabolism. For this reason, the offspring from mothers receiving either tap water, Cd, Zn or Cd + Zn during gestation and lactation periods were euthanized at PND21 and PND70. At the end of the lactation period (PND21), our results showed that exposure to Cd increased Cd accumulation and Zn depletion in the femur. Furthermore, calcium (Ca) level was reduced. At the molecular level, Cd induced an increase of MT-1 expression and caused an upregulation of ZIP2 accompanied with a down-regulation of ZnT5. Runx2, ALP, colα-1 and Oc mRNA levels were also decreased. In plasma, IGF-1 and osteocalcin concentrations were decreased. Further, Cd altered femoral growth by generating changes in the growth plate. Consequently, the toxic effect of Cd persisted at adult age (PND70) by decreasing bone volume (%BV/TV), bone mineral density (BMD) and Ca content and by increasing trabecular separation (Tb.Sp) in the distal femur. Interestingly, Zn supply provided total or partial corrections of several toxic effects of Cd. These data suggest that the increases of Zn bioavailability as well as the reduction of Cd accumulation in the femur following the changes in ZIP2 and ZnT5 expression are part of the mechanism involved in Zn protection against Cd toxicity on bone tissue.

Shoulder adhesive capsulitis: diagnostic value of active and passive range of motion with volume of gleno-humeral capsule as a reference.

BACKGROUND: The diagnosis of adhesive capsulitis is currently based on restricted range of motion (ROM) but its diagnostic value has only been rarely investigated. AIM: The aim of this study is to assess the diagnostic value of active global and passive gleno-humeral ROM to diagnose shoulder adhesive capsulitis. DESIGN: Cross-sectional descriptive study. SETTING: One French center for Rehabilitation Medicine. POPULATION: Patients referred for treatment of shoulder adhesive capsulitis in our center were included. Inclusion criteria were: shoulder pain; limitation of active global ROM (abduction or flexion <180°); limitation of passive gleno-humeral ROM (abduction or flexion <90° or 25% reduction at less of lateral rotation versus the opposite shoulder); no gleno-humeral arthropathy on radiography. METHODS: The volume of the gleno-humeral capsule was assessed during a procedure of arthro-distension. The reference criterion for adhesive capsulitis was a volume <12 mL. We analyzed the correlation between the parameters of mobility and the volume of the gleno-humeral capsule; and the positive predictive value (PPV) of inclusion criteria, with the reference criterion for the diagnosis of adhesive capsulitis. RESULTS: We included 38 patients. Passive gleno-humeral ROM in abduction only was correlated with volume of the gleno-humeral capsule: r=0.33, P=0.043. The PPV of inclusion criteria was 82% for the diagnosis of shoulder adhesive capsulitis. Rather than 90°, when we considered 80°, 60° and 40° as the threshold of passive gleno-humeral ROM in abduction, the PPV increased from 83% to 100%. CONCLUSIONS: Passive gleno-humeral ROM in abduction is correlated with volume of the gleno-humeral capsule. The PPV is high for active global and passive gleno-humeral ROM for diagnosis of shoulder adhesive capsulitis. CLINICAL REHABILITATION IMPACT: Limitation of active and passive shoulder ROM, especially passive abduction gleno-humeral, is a good criterion to diagnose shoulder adhesive capsulitis, in patients with shoulder pain and no gleno-humeral arthropathy on radiography.

Correction: Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis.

[This corrects the article DOI: 10.1371/journal.pone.0207441.].

Comparative study of psychometric properties of three assessment tools for degenerative rotator cuff disease.

OBJECTIVE:: To compare psychometric properties of Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Shoulder Pain and Disability Index (SPADI) and Constant-Murley scale, in patients with degenerative rotator cuff disease (DRCD). DESIGN:: Longitudinal cohort. SETTING:: One French university hospital. METHODS:: The scales were applied twice at one-week interval before physiotherapy and once after physiotherapy two months later. The perceived improvement after treatment was self-assessed on a numerical scale (0-4). The test-retest reliability of the DASH, SPADI and Constant-Murley scales was assessed before treatment by the intraclass correlation coefficient (ICC). The responsiveness was assessed by the paired t-test ( P < 0.05) and standardized mean difference (SMD). The correlation between the percentage of variation in scale scores and the self-assessed improvement score after treatment was measured by the Spearman coefficient. RESULTS:: Fifty-three patients were included. Twenty-six only were available for reliability. The test-retest reliability was very good for the DASH (ICC = 0.97), SPADI (0.95) and Constant-Murley (0.92). The scale score was improved after treatment for each scale ( P < 0.05). The SMD was moderate for the DASH (0.56) and SPADI (0.56) scales, and small for the Constant-Murley (0.44). The correlation between the percentage of variation in scores and self-assessed improvement score after treatment was high, moderate and not significant for the SPADI (0.59, P < 0.0001), DASH (0.42, P < 0.01) and Constant-Murley scales, respectively. CONCLUSION:: The test-retest reliability of the DASH, SPADI and Constant-Murley scales is very good for patients with DRCD. The highest responsiveness was achieved with the SPADI.