Denosumab use in osteogenesis imperfecta: an update on therapeutic approaches

Osteogenesis imperfecta (OI) is an inherited skeletal disorder that leads to bone fragility and multiple fractures. Given advances in the genetic understanding of existing phenotypes and newly discovered mutations, therapeutic management of OI has become challenging. Denosumab, a monoclonal antibody that inhibits the interaction between the receptor activator of nuclear factor kappa B ligand (RANKL) and its receptor RANK, has been approved to treat postmenopausal osteoporosis and emerged as an important therapy for malignancies and other skeletal disorders, including pediatric skeletal conditions such as OI. This review summarizes information about denosumab therapy in OI by exploring its mechanisms of action, main indications, and safety and efficacy. Several case reports and small series have been published about the short-term use of denosumab in children with OI. Denosumab was considered a strong drug candidate for OI patients with bone fragility and a high risk of fracture, particularly for patients with the bisphosphonate (BP)-unresponsive OI-VI subtype. The evidence for denosumab's effects in children with OI indicates that it effectively improves bone mineral density but not fracture rates. A decrease in bone resorption markers was observed after each treatment. Safety was assessed by tracking the effects on calcium homeostasis and reporting side effects. No severe adverse effects were reported. Hypercalciuria and moderate hypercalcemia were reported, suggesting that BPs be used to prevent the bone rebound effect. In other words, denosumab can be used as a targeted intervention in children with OI. The posology and administration protocol require more investigation to achieve secure efficiency.

[Validation of the ankylosing spondylitis quality of life questionnaire in Tunisian language]

The Ankylosing Spondylitis Quality of Life [ASQoL] questionnaire is a Wide-world used, unidimensional, disease-specific measure of quality of life. Arabic or Tunisian versions of ASQoL or any other quality of life index are not provided. To adapt the Ankylosing Spondylitis Qhality of life Questionnaire [ASQoL] for use in Tunisian and to test its reliability and validity. 99 patients who fulfilled the modified New York criteria for ankylosing spondylitis [AS] were included in this study [84 male and 15 female]. The translation process included the recent guidelines for cross-cultural adaptation. Reliability of the Tunisian version of the ASQoL was assessed by test-retest method [day 1 and day 10] and internal consistency using Cronbach's alpha coefficient. For construct validity, ASQoL scores were correlated with specific instruments of AS. The mean age of patients was 38.35 years +/- 12.26 [18- 73] and the mean disease duration was 11.3 years +/- 9.4 [0.6 - 40]. The mean time to complete the questionnaire was 5 minutes. Reproducibility was good with no significant difference between ASQoL0 [mean score = 9.8 +/- 5.04] and ASQoL10 [mean score = 9.46 +/- 5.89] as well as the statically significant positive correlation intra-class coefficient: 0.87 [IC 95%: 0.79-0.92]. Internal consistency was good [Cronbach: 0.933; IC95%=0.86-0.95]. ASQoL was significantly correlated with BASDAI [p<0.001], BASFI [p<0.001], BASG-s [p<0.001], BASMI [p=0.026], MASES [p=0.024] and all items of SF-36.Validation of the ASQoL for use in Tunisia was successful. The results of the present study indicate that the Tunisian version for ASQoL is reliable and valid

Health-related quality of life assessment on 100 tunisian patients with ankylosing spondylitis using the sf-36 survey

The main objective of the study was to examine the self reported health status in patients with ankylosing spondylitis [AS] compared with the general population and the secondary objective [in the AS group] was to study the association between health status, demographic parameters, and specific disease instruments in AS. A cross sectional study of 100 AS patients recruited between 2006 and 2009 at the Department of Rheumatology. Health status was assessed by using the SF-36 health questionnaire in patients with AS. Demographic characteristics and diseasespecific instruments were also examined by the questionnaire. A sample of 112 healthy individuals was also surveyed using the SF- 36 health questionnaire. This study showed a great impairment in the quality of life of patients with AS involving all scales. All male patients with AS reported significantly impaired health-related quality of life on all items of the SF-36 compared with the general population whereas female patients reported poorer health on three items only, namely physical functioning, general health and bodily pain. Mental health was mostly affected than physical role. The physical role was significantly higher in patients with high education level than in patients with low education level [p=0.01]. Physical functioning was better in employed patients. All scales of SF-36 were correlated with BASFI, BASDAI and BAS-G. Only physical functioning and general health were correlated with BASMI. Impairment in the quality of life can be significant when suffering from AS, affecting mental health more than physical health. Among disease parameters, functional impairment, disease activity, mobility limitation, and spinal pain were the most associated factors resulting to the deterioration of quality of life

[Rhumatologic disorders of Sarcoidosis]

Sarcoidosis is a systemic granulomatous disease of unknown etiology. It has various clinical features. The most commonly affected organs are the lung, the lymph nodes, the eyes and the skin. Involvement of the musculoskeletal system is far less common and may be inaugural. Articular involvement is dominated by Lofgren syndrome and acute polyarthritis. Abarticular manifestations are often confounded with arthritis. Bone locations are dominated by unknown and can appear as 3 clinical features: spread form, myositique form or pseudotumoral form. Calcium balance disturbances are dominated by hypercalcemia which is often asymptomatique, but sometimes it reveal the sarcoidosis. Treatment of rheumatologic disorders often involves non steroidal anti-inflammatory drugs, corticosteroids and methotrexate. Biological therapies such as the anti-TNFalpha and the anti-CD20 were showed to be effective in some case reports of severe and refractory disease

Non contiguous multilevel spondylitis: an exceptional presentation of spinal brucellosis

The aim of this study was to describe the imaging features of multilevel brucellar spondylitis and discuss the diagnostic challenges The authors report describes one case of noncontiguous synchronous multifocal involvement of thoracic and lumbar spine. Brucellosis is a zoonosis of worldwide distribution, relatively frequent in Mediterranean countries and in the Middle East that can involve many organs and tissues. The spine is the most common site of musculoskeletal involvement, but multilevel involvement is uncommon and only ten cases were reported in literature. Although it is an exceptional form, multifocal brucellar spondylitis is worth to be known to avoid diagnostic mistakes

[Validation of the Tunisian versions of bath ankylosing spondylitis functional index [BASFI] and disease activity index [BASDAI]]

The Bath Ankylosing Spondylitis Functional Index [BASFI] and the Bath Ankylosing Spondylitis Disease Activity [BASDAI] are the most commonly used instruments to evaluate respectively functioning and disease activity in ankylosing spondylitis [AS]. The aim of this study was to translate, adapt and validate these instruments into the Tunisian language. The studied population consisted of 68 AS patients [59 males and 9 females]. Their mean age was 37.9 years [range: 18-76]. The mean disease duration was 13.6 years [range: 1-40].After translation and retranslation the BASFI and BASDAI questionnaires were administrated to the patients and tested for reliability, internal consistency and construct validity. The reproducibility of the indices BASFI and BASFAI was good, the intraclass correlation coefficient for reliability was 0.96 [CCI: 0.93-0.97] for the BASFI and 0.93 [CCI: 0.90 -0.97] for the BASDAI, and the coefficient of internal consistency [Cronbach's alpha] was 0.91 for BASFI and 0.90 for BASDAI. Concerning construct validity, both questionnaires were significantly correlated to each other, to the disease-specific instruments [BASG-s, BASMI, BASRI, ASQoL] and to all domains of the SF-36. The Tunisian versions of the BASFI and the BASDAI preserve the metrological properties of the original versions and were easy to use for the assessment of disease status in ankylosing spondylitis

[Osteopenia for patients with crohn diseas]

Osteoporosis and osteopenia are frequently reported during chronic inflammatory bowel diseases, particularly in Crohn disease [CD]. To determine the frequency of osteoporosis and osteopenia of patients with CD and to study associated risk factors. A forward-looking study was performed about 56 cases of CD, 34 men and 22 women, aged 32+10.4 years [18-54 years], with no other disorders affecting osseous metabolism. A biphotonic X-rays absorptiometry densitometry [DEXA] was performed at femoral neck and lumbar spine. A multivariate statistical analysis was performed to check for factors contribiuting in lowing osseous mineral density. Osteoporosis and osteopenia are noticed with respective frequency of 35.7%and 23.2%. A statistically significant association is found between low osseous density on one hand and physical mass index [IMC], localisation on large bowel of the disease and corticotherapy on the other hand. The IMC was a risk factor independant from the two other factors. Under nutrition, with IMC<18 kg/m c, was observed at 21 patients. It was associated to a pathological densitometry in 76.2%of cases, versus 48.6%in patients having an IMC>18 kg/m c [p=0.03, Odds ratio 3.4]. Among risk factors involved in the osteoporosis during CD, the nutritional status plays an important role which must be taken into account in the treatment of these patients

Common lumbosciatic of the elderly. about 67 cases

The common lombosciatic is a disease observed at all ages. To the elderly, clinical data, treatment, clinical outcome and prognosis present sometimes some peculiarities. Aim: Report of lombosciatic in the elderly. It is a retrospective study including 67 cases of sciatica concerning old patients over 65 years presenting with common lombosciatica, hospitalized between January the 1-st, 2000 and December 31st, 2004. The mean age of our patients is of 71.2 years, sex ratio female / male of 1.88. A chronic lumbago is found at 16.34% of our patients and a starting factor pains in 14.3% of cases. Pain is of progressive installation in 93.4% of cases. Mechanical in 77.5% of cases and impulsive in 55% of cases. Sciatica was unilateral in 67.3% of cases and interesting the root L 5 in 40.8% of cases. Physical exam find a painless attitude in 26.5% of cases and a spasm of spinal muscles in 65.3%. The average of schober index is of 2.4 cms + 1.18. Lasegue is present in 36.7% of cases. Neurological exam find overdrawn signs in 8% of cases, sensory signs in 61.2% of cases. No cauda equine syndrome was individualized in our series. Lumbar spine X-rays, made in 98% of cases, show a L5-S1 disc impairment in 83.6% of cases, a scoliotic attitude in 22.4% of cases, a spondylolithesis of L4L5 in 26,5% of cases and lumbar cannal stenosis in 12.2% of cases. Lumbar densitometry, realized in 22.4% of cases, shows a herniated disc in 27.2% of cases, and a lumbar canal stenosis in 27.2% of cases. The MRI, made once, was normal. During their hospitalization, 87.7% of patients received NSAID's, 18.4% of them analgesics drugs [landing I, II, III] and 79.6% epidurals infiltrations. All our patients observed bed rest. A physiotherapy was prescribed for 44.9% of them. A good outcome was quickly noticed in 85.7% of the patients. A therapeutic failure was observed at 14.3%. 6% underwent surgery. Only 10,2% of the non operated patient had pain recurrence. Nowadays sciatica is a frequent pathology either in young or in geriatric population. Nevertheless it is necessary to eliminate a tumoral or infectious sciatica that can be misleading by the condition of the old age and by the frequent associated pathologies at such age

[Septic oligoarthritis as a complication of rhumatoid arthritis - a case report]

We present the case a 53-year-old patient followed-up since 1999, for erosive AR treated with methotrexate and glucocorticoids. In April 2000, he had an arthritis of the right knee. The identification of an enterobacter in blood culture, and synovial biopsy results permitted the diagnosis of septic arthritis. After 23 days of antibioterapy treatment, the patient had an arthritis of the left knee. The infectious origin was confirmed by synovial biopsy. The course was better after adaptation of the antibiotics. Septic arthritis is then a serious complication of AR. It requires a fast and multidisciplinary management. It can be threatenig in fragile and immunocompromised patients. The functional prognosis is especially compromised in polyarticular septic arthritis