Osteoimmunology in mucopolysaccharidoses type I, II, VI and VII. Immunological regulation of the osteoarticular system in the course of metabolic inflammation.

BACKGROUND: Mucopolysaccharidoses (MPSs) are rare genetic diseases caused by a deficient activity of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. These metabolic blocks lead to the accumulation of GAGs in various organs and tissues, resulting in a multisystemic clinical picture. The pathological GAG accumulation begins a cascade of interrelated responses: metabolic, inflammatory and immunological with systemic effects. Metabolic inflammation, secondary to GAG storage, is a significant cause of osteoarticular symptoms in MPS disorders. OBJECTIVE AND METHOD: The aim of this review is to present recent progress in the understanding of the role of inflammatory and immune processes in the pathophysiology of osteoarticular symptoms in MPS disorders and potential therapeutic interventions based on published reports in MPS patients and studies in animal models. RESULTS AND CONCLUSIONS: The immune and skeletal systems have a number of shared regulatory molecules and many relationships between bone disorders and aberrant immune responses in MPS can be explained by osteoimmunology. The treatment options currently available are not sufficiently effective in the prevention, inhibition and treatment of osteoarticular symptoms in MPS disease. A lot can be learnt from interactions between skeletal and immune systems in autoimmune diseases such as rheumatoid arthritis (RA) and similarities between RA and MPS point to the possibility of using the experience with RA in the treatment of MPS in the future. The use of different anti-inflammatory drugs requires further study, but it seems to be an important direction for new therapeutic options for MPS patients.

Pyknodysostosis: imaging and laboratory observations.

Pyknodysostosis is a rare form of sclerosing bone dysplasia with autosomal recessive inheritance. Affected members of two families were assessed as follows: three patients underwent densitometry measurements and bone scans; four patients underwent magnetic resonance imaging (MRI) and an immunological investigation, as well as a detailed endocrinological and biochemical laboratory review. Densitometry measurements revealed values of up to 291% of age-matched normal controls; this increased bone density was mainly in the trabecular bone and not in the cortical bone. The MRI showed the cortex to be of normal thickness, whereas the increase in trabecular bone limited the space within the medullary canal. Bone scans and single photon emission computerized tomography in three patients showed an increased uptake of [99mTc]methylene diphosphonate of up to 538% of age-matched controls, which reflected the increased bone density. Monocyte function tests demonstrated a normal phagocytic capacity, but their killing activity was impaired. Interleukin-1 secretion was also impaired, which may point to the pathogenesis of the disease, in view of its function as an osteoclast activator and its role in bone resorption.