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.

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.

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.

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.

What are the predictors of clinical success after percutaneous vertebroplasty for osteoporotic vertebral fractures?

OBJECTIVES: Osteoporotic vertebral fractures are responsible for acute pain and disability that may persist for more than 2 months. We wanted to identify predicting factors for mid-term outcome after vertebroplasty. METHODS: We included consecutive patients who underwent vertebroplasty for fragility fractures with persistent and intense pain between January 2014-June 2016. Outcome was assessed by an independent clinician after 1 month using a standardized questionnaire. Patients were classified as having either a favorable or a poor outcome. Presence of an intravertebral cleft and bone oedema mean signal intensity was assessed by an independent radiologist blinded to the clinical data. Pre-intervention clinical or radiological factors were analysed as predictors for outcome. RESULTS: In the 78 included patients (females 71%, age 75 ± 8.3 years), 61.5% had a favourable outcome. When vertebroplasty was performed within 2 months after fracture, the outcome was favourable in 19 patients (39.6%) and poor in five (16.7%; estimate for favourable outcome: OR = 4.1, 95% CI 1.2-13.8, p = 0.021). Absence of intravertebral cleft on pre-intervention imaging was also a predictor of favourable outcome (OR = 3.7, 95% CI 1.2-11.8, p = 0.024). On pre-intervention MRI, vertebral body oedema intensity signal did not influence the outcome. CONCLUSIONS: In patients with persistent and intense pain after an osteoporotic vertebral fracture, early intervention and absence of intravertebral cleft were predictors of favourable outcome at 1 month after vertebroplasty. KEY POINTS: • Performing vertebroplasty within 2 months following a fragility fracture increases success rate. • Presence of an intravertebral cleft at baseline is a predictor of poor mid-term outcome. • A pre-intervention MRI should be performed to ascertain the indication of vertebroplasty.

Treacher Collins syndrome: a clinical and molecular study based on a large series of patients.

PURPOSE: Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. METHODS: We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. RESULTS: We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. CONCLUSION: Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.

Phase III, randomized, double-blind, placebo-controlled trial of topical 2 % lidocaine for the prevention and treatment of oral mucosal pain in children.

OBJECTIVES: The aim of this study was to assess the efficacy in pain reduction of topical 2 % lidocaine compared to a placebo cream in children with oral mucosal lesions due to trauma or aphthous ulcers or in the prevention of clamp placement pain. MATERIALS AND METHODS: The design was a double-blind, randomized, placebo-controlled, four-center trial on 64 patients. Pain intensity and relief were measured using a 100-mm visual analog scale (VAS). One-tailed Student's t test and ANOVA were used for statistical analyses. RESULTS: Independent of the pain origin, application of 2 % lidocaine cream led to a mean reduction in VAS pain intensity of 19.7 mm ± 18.3, which was significantly greater than that obtained with the placebo cream (p = .025). Analyses showed a statistically significant efficacy of the 2 % lidocaine cream (p < .0001). Its efficacy was not associated to any local or systemic adverse drug reaction, as reported by the patients. As the most important population represented in our patients was children whom a rubber dam clamp was placed, we also specifically analysed this population, and we were able to demonstrate a significantly greater efficacy of the 2 % lidocaine cream on the pain caused by the rubber dam clamp placement in comparison to the placebo cream (p < .005). CONCLUSIONS: A significant reduction in pain intensity occurred after application of 2 % lidocaine cream, and the effect was significantly greater than that obtained with the placebo cream. Considering the study's limitations, this product appears safe for use in children. CLINICAL RELEVANCE: For painful benign lesions of the oral mucosa (trauma or aphthous ulcers) or for preventing painful iatrogenic procedures such as rubber dam clamp placement, it is essential to treat or prevent pain onset, especially in the pediatric population for whom a painful experience could end in refusal of dental care. Application of a topical anesthetic in this specific situation is of particular interest, as is defining its efficacy and safety.

Long-Term Differential Effects of Gastric Bypass and Sleeve Gastrectomy on Bone Mineral Density.

Context: The association of obesity with bone fragility fractures is complex and non-linear. Despite good efficacy on weight loss, bariatric surgery (BS) is also associated with bone loss. However, we lack information on risk factors of the long-term deleterious effects of BS on the skeleton. Objective: We aimed to assess the factors associated with low bone mineral density (BMD) performed a long time after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Methods: This cross-sectional study involved patients at a long distance from their BS that underwent dual-energy x-ray absorptiometry (DXA) with biological factors (vitamins, micronutrients, bone and inflammation biomarkers). Simple and multiple linear models (stepwise and parsimony approach) were developed. Results: A total of 131 patients (91 RYGB, 40 SG) underwent DXA (51.8 ± 11.08 years, 87.8% women). At a mean of 6.8 ± 3.7 years after surgery, the mean weight loss was -28.6 ± 9.6%, and only 6 patients (5.7%) had a T-score less than or equal to -2.5. On univariate analysis, BMD was lower in the RYGB than in the SG group (P < .001) at all sites, despite similar fat and fat-free mass and weight loss. Serum parathyroid hormone and phosphate levels were higher in RYGB than SG patients. A total of 10.1% of patients showed vascular calcifications. On multivariable analysis, BMD remained different between surgery groups after adjustment for age, body mass index, ethnicity, and sex. The model-adjusted R 2 values were 0.451 for the total hip; 0.462 the femoral neck, and 0.191 the lumbar spine for the inflammation model; 0.458, 0.462, and 0.254, respectively, for the bone marker model; and 0.372, 0.396, and 0.142 for the vitamin model. Serum zinc, ferritin, and uric acid levels were the markers associated with BMD to a low extent. Conclusion: BMD differed depending on the BS procedure. A few biological markers may be associated weakly with BMD well after the surgery.

Evaluation of bone density and microarchitecture in adult patients with X-linked hypophosphatemic rickets: A pilot longitudinal study.

X-linked Hypophosphatemia (XLH) is the most common type of inherited rickets. Although the clinical features are well characterized, bone structure, mineralization, and biomechanical properties are poorly known. Our aim was to analyze bone properties in the appendicular and axial skeleton of adults with XLH. In this observational case-control study, each affected patient (N = 14; 9 females; age 50 ±â€¯15 years) was matched by sex, age and body mass index to a minimum of two healthy controls (N = 34). Dual-energy X-ray Absorptiometry (DXA) analyses revealed that areal bone mineral density (aBMD) was higher in XLH patients at the lumbar spine (Z score mean difference = +2.47 SD, P value = 1.4 × 10-3). Trabecular Bone Score was also higher at the lumbar spine (P value = 1.0 × 10-4). High Resolution peripheral Quantitative Computed Tomography (HRpQCT) demonstrated that bone cross-sectional area was larger at the distal radius (P value = 6 × 10-3). Total and trabecular volumetric BMD were lower at both sites. Trabecular bone volume fraction was also lower with fewer trabecular numbers at both sites. However, bone strength evaluated by micro-finite element analyzes revealed unaffected bone stiffness and maximum failure load. Evaluation of bone mineralization with aBMD by DXA at the distal radius correlated with vBMD by HRpQCT measurements at both sites. PTH levels were inversely correlated with trabecular vBMD and BV/TV at the tibia. We then followed a subset of nine patients (median follow-up of 4 years) and reassessed HRpQCT. At the tibia, we observed a greater decrease than expected from an age and sex standardized normal population in total and cortical vBMD as well as a trabecularization of the cortical compartment. In conclusion, in adult patients with XLH, bone mineral density is high at the axial skeleton but low at the appendicular skeleton. With time, microarchitectural alterations worsen. We propose that noninvasive evaluation methods of bone mineralization such as DXA including the radius should be part of the management of XLH patients. Larger studies are needed to evaluate the clinical significance of BMD changes in XLH patients under conventional or targeted therapies.

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.

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.

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.

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.

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.

Does hormone replacement therapy prevent lateral rotatory spondylolisthesis in postmenopausal women?

PURPOSE: Degenerative scoliosis usually begins at menopause and lateral rotatory olisthesis (LRO) might be a triggering factor in the onset of degenerative scoliosis in postmenopausal women. We set out to evaluate the influence of hormone replacement therapy (HRT) on degenerative scoliosis and on LRO. METHODS: A cross-sectional study was conducted in 146 postmenopausal women: 75 women had received HRT for more than 1 year (HRT > 1) and 71 women had never received HRT or less than 1 year (HRT < 1). Scoliotic curve, LRO, sacral slope, lordosis, kyphosis were measured. The excess risk of LRO associated with age, BMI, isometric strength of brachial biceps, bone mineral density, lean mass and HRT was evaluated using a multiple logistic regression model. RESULTS: No difference was found in sacral slope, lumbar lordosis or thoracic kyphosis between both groups or in the presence of scoliosis. The prevalence of LRO was significantly lower in HRT >1 than HRT <1 (8 vs. 30%) while the risk was dependent on age, HRT and their interaction. LRO increased with age only in HRT <1 (11% when aged ≤66 years vs. 39% when aged >66 years, p = 0.013), whereas the prevalence of LRO remained stable in HRT >1. CONCLUSIONS: LRO was significantly lower in women who received HRT. The excess risk of LRO was dependent on both age and HRT status. These findings suggest that HRT might prevent the onset of LRO, and therefore might contribute to the prevention of low back pain.

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.

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.

Effects of risedronate in Runx2 overexpressing mice, an animal model for evaluation of treatment effects on bone quality and fractures.

Young mice overexpressing Runx2 specifically in cells of the osteoblastic lineage failed to gain bone mass and exhibited a dramatic increase in bone resorption, leading to severe osteopenia and spontaneous vertebral fractures. The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Four-week-old female Runx2 mice received Ris at 2 and 10 µg/kg subcutaneously twice a week for 12 weeks. Runx2 and wild-type mice received vehicle (Veh) as control. We measured the number of new fractures by X-ray and bone mineral density (BMD) by DEXA. We evaluated bone quality by histomorphometry, micro-CT, and Fourier transform infrared imaging (FTIRI). Ris at 20 µg/kg weekly significantly reduced the average number of new vertebral fractures compared to controls. This was accompanied by significantly increased BMD, increased trabecular bone volume, and reduced bone remodeling (seen in indices of bone resorption and formation) in the vertebrae and femoral metaphysis compared to Runx2 Veh. At the femur, Ris also increased cortical thickness. Changes in collagen cross-linking seen on FTIRI confirmed that Runx2 mice have accelerated bone turnover and showed that Ris affects the collagen cross-link ratio at both forming and resorbing sites. In conclusion, young mice overexpressing Runx2 have high bone turnover-induced osteopenia and spontaneous fractures. Ris at 20 µg/kg weekly induced an increase in bone mass, changes in bone microarchitecture, and decreased vertebral fractures.