Paget disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. The main alteration resides in osteoclasts that increase in size, number and activity. Many osteoclasts have cytoplasmic inclusions that have been associated with protein aggregates, increasing the evidences of a possible deregulation of autophagy in the development of the PDB. Autophagy starts with encapsulation of the target into a double-membrane-bound structure called an “autophagosome.” It has been reported that at least 18 ATG genes (autophagy-related genes) are involved in autophagosome formation. We have studied the distribution of genotypes of the ATG2B rs3759601, ATG16L1 rs2241880, ATG10 rs1864183 and ATG5 rs2245214 polymorphisms in a Spanish cohort of subjects with PDB and compared with healthy subjects. Our results show that being a carrier of the C allele of the ATG16L1 rs2241880 and the G allele of ATG5 rs2245214 polymorphisms were associated with an increased risk of developing PDB, whereas being a carrier of the T allele of ATG10 rs1864183 polymorphism decreased the risk of suffering the disease in our series. This is the first report that shows an association between autophagy and Paget Disease of Bone and requires further confirmation in other series.

Age-related macular degeneration (AMD) is a complex, multifactorial and progressive retinal disease affecting millions of people worldwide. In developed countries, it is the leading cause of vision loss and legal blindness among the elderly. Although the pathogenesis of AMD is still barely understood, recent studies have reported that disorders in the regulation of the extracellular matrix (ECM) play an important role in its etiopathogenesis. The dynamic metabolism of the ECM is closely regulated by matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). The present review focuses on the crucial processes that occur at the level of the Bruch’s membrane, with special emphasis on MMPs, TIMPs, and the polymorphisms associated with increased susceptibility to AMD development. A systematic literature search was performed, covering the years 1990–2020, using the following keywords: AMD, extracellular matrix, Bruch’s membrane, MMPs, TIMPs, and MMPs polymorphisms in AMD. In both early and advanced AMD, the pathological dynamic changes of ECM structural components are caused by the dysfunction of specific regulators and by the influence of other regulatory systems connected with both genetic and environmental factors. Better insight into the pathological role of MMP/TIMP complexes may lead to the development of new strategies for AMD treatment and prevention.

Paget’s disease of bone (PDB) is a common skeletal disorder characterised by focal abnormalities of increased and disorganised bone turnover. Genetic factors play a central role in the pathogenesis of PDB but environmental factors also contribute. Measles virus (MV), respiratory syncytial virus (RSV) and canine distemper virus (CDV) have all been implicated as potential disease triggers but the data are conflicting. Since chronic paramyxovirus infection with measles is known to be accompanied by increased production of antiviral antibodies, we have analysed circulating concentrations of antibodies to MV, CDV, and RSV as well as mumps, rubella and varicella zoster virus (VZV) in 463 patients with PDB and 220 aged and gender-matched controls. We also studied the relation between viral antibody concentrations and various markers of disease severity and extent in 460 PDB patients. A high proportion of cases and controls tested positive for antiviral antibodies but there was no significant difference in circulating antibody concentrations between PDB cases and controls for MV, CDV, RSV, rubella or VZV. However, mumps virus antibody levels were significantly higher in the PDB cases (mean ± SD = 3.1 ± 0.84 vs. 2.62 ± 0.86. p < 0.001). There was no association between disease severity and circulating antibody concentrations to any of the viruses. In conclusion, we found no evidence to suggest that PDB is associated with abnormalities of immune response to measles or other paramyxoviruses, although there was evidence of a greater antibody response to mumps. The results do not support that hypothesis that PDB is associated with a persistent infection with measles or other paramyxoviruses.