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.

[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