M. Cohen-Solal

Annexin 5 overexpression increased articular chondrocyte apoptosis induced by basic calcium phosphate crystals

Objectives: Basic calcium phosphate (BCP) crystals (octacalcium phosphate (OCP), carbapatite (CA) and hydroxyapatite (HA)) are associated with severe forms of osteoarthritis. In advanced osteoarthritis, cartilage shows chondrocyte apoptosis, overexpression of annexin 5 (A5) and BCP crystal deposition within matrix vesicles. We assessed in vitro whether BCP crystals and overexpression of A5 increased chondrocyte apoptosis. Methods: Apoptosis was induced by BCP crystals, tumour necrosis factor (TNF)-α (20 ng/ml) and Fas ligand (20 ng/ml) in normal articular chondrocytes (control) and in A5 overexpressed chondrocytes, performed by adenovirus infection. Apoptosis was assessed by caspase 3 (Cas3) activity, and DNA fragmentation. Results: All BCP crystals, TNF-α and Fas ligand induced chondrocyte apoptosis as demonstrated by decreased cell viability and increased Cas3 activity and DNA fragmentation. TUNEL (terminal deoxyribonucleotide transferase-mediated dUTP nick end-labelling)-positive staining chondrocytes were increased by OCP (12.4 (5.2)%), CA (9.6 (2.6)%) and HA (9.2 (3.0)%) crystals and TNF-α (9.6 (2.4)%) stimulation compared with control (3.1 (1.9)%). BCP crystals increased Cas3 activity in a dose-dependent fashion. BCP-crystal-induced chondrocyte apoptosis was independent from TNF-α and interleukin-1β pathways but required cell-crystal contact and intralysosomal crystal dissolution. Indeed, preincubation with ammonium chloride, a lysosomal inhibitor of BCP crystal dissolution, significantly decreased BCP-crystal-induced Cas3 activity. Finally, overexpression of A5 enhanced BCP crystal- and TNF-α-induced chondrocyte apoptosis. Conclusions: Overexpression of A5 and the presence of BCP crystals observed in advanced osteoarthritis contributed to chondrocyte apoptosis. Our results suggest a new pathophysiological mechanism for calcium-containing crystal arthropathies.

Assessment of dynamic humeral centering in shoulder pain with impingement syndrome: a randomised clinical trial

Objectives Treatment for degenerative rotator cuff disease of the shoulder includes physiotherapy. Dynamic humeral centering (DHC) aims at preventing subacromial impingement, which contributes to the disease. The goal of this study was to assess the effectiveness of DHC. Method 69 patients with shoulder pain and impingement syndrome were prospectively included in a single-centre randomised trial with a 12-month follow-up. Patients and assessor were blinded to the study hypothesis and treatment, respectively. DHC and non-specific mobilisation as control were performed for 6 weeks, in 15 supervised individual outpatient sessions, and patients performed daily home exercises. The planned primary outcome was the Constant score including subscores for pain, activity, mobility and strength at 3 months. Secondary outcomes were the Constant score and subscores at 12 months, and medication use for pain at 3 and 12 months. Results The DHC group did not differ from the control group in the total Constant score at 3 months. However, the DHC group showed a higher Constant subscore for pain (12.2 (SD 2.8) vs 9.9 (2.9), least square means difference 2.1, 95% CI 0.7 to 3.5, p=0.004). At 3 months, the DHC group also showed a higher rate of no medication use (96.7% vs 71%, proportional difference 25.7, 95% CI 3.7 to 51.9, p=0.012). There was no other intergroup difference. Conclusions There was no difference in the total Constant score between DHC and controls. However, pain was improved at 3 months after DHC. The differences found in subscores for pain should be explored in future studies. Trial registration clinicaltrials.gov Identifier: NCT 01022775.

Efficacy of a functional restoration program for chronic low back pain: prospective 1-year study.

OBJECTIVE To evaluate the efficacy of a functional restoration program for patients with chronic low back pain, using overall disability and work ability as the primary evaluation criteria. PATIENTS AND METHODS We prospectively studied patients aged 18 years or older who had been on sick leave because of nonspecific low back pain for at least 3 months and whose job position was still open. The program was delivered on a day-hospital basis 5 days a week for 5 weeks. Patients were followed up for 1 year. RESULTS We included 39 patients, 11 females and 28 males with a mean (± SD) age of 43 ± 8 years and a mean sick-leave duration of 10 ± 7 months. After 1 year, 26 (67%) patients reported improvements and 25 (64%) had returned to work. Compared to the year before the program, the number of sick leave days was decreased by 51% (120 ± 140 vs. 244 ± 114, P < 0.05). The work-and-leisure-activities subscore of the validated French version of the Dallas Pain Questionnaire (DRAD) was significantly improved (57 ± 24 vs. 70 ± 17 at baseline, P < 0.05). The patients still on sick leave after 1 year were older and had greater alterations in baseline DRAD subscores for anxiety/depression and daily activities, compared to the patients who had returned to work. CONCLUSIONS Our functional restoration program was effective and allowed two-thirds of patients to resume work. Factors associated with failure to resume work were well-known correlates of chronicity. Our results support the use of functional restoration programs in patients with incapacitating low back pain. They suggest that functional restoration may deserve to be started earlier, after only 3 months with chronic pain, in patients who are unable to work.

Plasma bone-specific alkaline phosphatase changes in hemodialysis patients treated by alfacalcidol.

Vitamin D derivatives correct high bone remodeling by decreasing plasma iPTH concentration in uremic patients with secondary hyperparathyroidism. However, without bone biopsy, plasma iPTH alone might not provide sufficient information regarding vitamin D-induced bone changes. Plasma bone-specific alkaline phosphatase (bAP) seems more sensitive than iPTH in assessing the degree of bone remodeling. We prospectively studied the evolution of iPTH and bAP in 14 adult hemodialysis patients treated for 1 year by i.v. alfacalcidol pulses. The mean total alfacalcidol dose was 0.08 +/- 0.02 g/kg/week. Ten patients completed the study, 2 patients had to be parathyroidectomized before week 24 because of hypercalcemia and uncontrolled hyperphosphatemia, and 2 other patients died before week 36. Mean iPTH levels diminished from 826 +/- 300 pg/ml (range 507 - 1,500 pg/ml) at baseline to 436 +/- 371 pg/ml (range 18 - 1,095 pg/ml) after 52 weeks of treatment (48% of decrease). Only 2 patients normalized plasma iPTH levels while 8/10 normalized bAP. Five patients remained with plasma iPTH concentrations higher than 5-fold the normal value. In contrast, plasma bAP levels declined from 47.6 +/- 32.2 ng/ml (range 15.4 - 130.0 ng/ml) at baseline to 17.8 +/- 9.9 ng/ml (range 8.0 +/- 38.0 ng/ml) at week 52 (63% of decrease). Bone histomorphometry was available in 6 patients after 15.8 +/- 5.1 months of alfacalcidol treatment. None of them met the criteria of adynamic bone disease as they had increased bone resorption and marrow bone fibrosis. Bone formation rate was normal in 2 patients and unmeasurable in the other 4. Two patients showed signs of osteomalacia. In conclusion, alfacalcidol preferentially reduced bone formation rate rather than the other histological parameters of secondary hyperparathyroidism. It reduced plasma bAP more efficiently than iPTH.

SAT0293 Hip Fractures in Patients with Dialysis: The impact of Dementia

Background Hip fractures (HF) are associated with significant morbidity and are further increased in patients with chronic renal failure (CRF). Higher morbidity in dialysis patients is related to several risk factors that are associated. Dementia is an associated risk factor for HF in the general population. Objectives We here aimed to describe the impact of dementia in FH in dialysis patients and assess if dementia is an additional risk factor of HF in patients with CRF. Methods Data are obtained from the National Database of Hospitalizations. In order to avoid the possibility of a high incidence based in single year, data were extracted over the period 2011-2013. Three populations of subjects aged 60 and over were extracted and analyzed: population with hip fracture, population in dialysis and population of demented patients (whatever the reason for the hospitalization whether or not in connection with dementia). These populations were crossed to estimate the fracture risk based on the presence of dementia or dialysis, adjusted for age and sex. The fracture risk was calculated using a multiple logistic regression model. Results Over the period 2011 to 2013, 213 180 patients experienced a hip fracture (70% women), 660 434 patients were diagnosed for dementia (64% women) and 47 430 patients were on dialysis (39% women). There was an effect of age and gender on the incidence of fractures and dementia. In dialysis patients, the risk of HF was significantly higher in patients with dementia compared to those without dementia: OR 1.99 [95% CI: 1.66-2.38], this being the same for men (OR 2.37 [1.81-3.05]) and women (OR 2.56 [1-97-3.29]) in each age categories. However, in patients with dementia, the fracture risk is independent of dialysis (OR: 1.25 [0.99-1.59]) in each gender and age categories. Moreover, the risk of dementia is not increased by dialysis in this population with HF (OR 1.52 [0.77-3]) after adjustment for age and gender. Conclusions Dementia significantly increases the risk of hip fracture in dialysis patients compared to the patients without dementia. However, this risk is the same than in demented patients whether in dialysis or not. These results highlight dementia as a major risk factor for FH in dialysis and points out the necessity of prevention to avoid hip fractures. Disclosure of Interest None declared

Vertebroplastie - cyphoplastie : indications et resultats a court et moyen termes

Objectifs Connaitre la frequence des tassements vertebraux asymptomatiques. Savoir poser l’indication d’une IRM rachidienne. Savoir reconnaitre un tassement vertebral recent. Savoir poser l’indication d’une vertebroplastie. Savoir orienter vers une prise en charge medicale. Points cles Deux tiers des tassements vertebraux sont pas ou peu douloureux. Demander un complement d’investigations s’il existe des signes cliniques ou radiologiques de pathologies malignes. Les tassements recents sont reconnus par un hypersignal en T2 sur l’IRM. Une vertebroplastie est indiquee si le risque de complications de decubitus est eleve, s’il existe un tassement osteoporotique instable ou si l’allure du tassement est suspect. Traitement local complementaire d’un traitement medical a visee anti-fracturaire. Resume Les tassements vertebraux se traduisent par douleurs aigues et chroniques. Seulement 1/3 des patients avec fracture vertebrale souffre de douleur en aigu. Celles-ci peuvent etre sources de handicap et morbidite importantes a court et long terme. La vertebroplastie a ete developpee dans un but a la fois antalgique et mecanique. Elle reduit considerablement la douleur de nombreuses pathologies vertebrales : tassement vertebral d’origine osteoporotique ou malin, hemangiome ou osteonecrose vertebrale. L’antalgie est obtenue dans 60 a 100 % si des criteres precis sont respectes comme le caractere recent (environ 3 mois). La contribution de l’IRM est fondamentale pour les tassements uniques et encore davantage en cas de tassements multiples, et recherchera la presence d’un hypersignal en T2. La mobilite est egalement amelioree chez 30 a 100 % des patients en reduisant les complications de decubitus a court terme et les complications statiques en cas de tassements a l’etage dorsal. Elle constitue un traitement local complementaire au traitement medical a visee anti-fracturaire.