Abstract
Osteocytes are terminally differentiated osteoblasts embedded within the bone matrix and key orchestrators of bone metabolism. However, they are generally not characterized by conventional bone histomorphometry because of their location and the limited resolution of light microscopy. OI is characterized by disturbed bone homeostasis, matrix abnormalities and elevated bone matrix mineralization density. To gain further insights into osteocyte characteristics and bone metabolism in OI, we evaluated 2D osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging in transiliac bone biopsy samples from children with OI type I (n = 19) and age-matched controls (n = 24). The OLS characteristics were related to previously obtained, re-visited histomorphometric parameters. Moreover, we present pediatric bone mineralization density distribution reference data in OI type I (n = 19) and controls (n = 50) obtained with a field emission scanning electron microscope. Compared to controls, OI has highly increased OLS density in cortical and trabecular bone (+50.66%, +61.73%; both p < 0.001), whereas OLS area is slightly decreased in trabecular bone (−10.28%; p = 0.015). Correlation analyses show a low to moderate, positive association of OLS density with surface-based bone formation parameters and negative association with indices of osteoblast function. In conclusion, hyperosteocytosis of the hypermineralized OI bone matrix associates with abnormal bone cell metabolism and might further impact the mechanical competence of the bone tissue.
Highlights
In recent years, the central role of osteocytes in orchestrating skeletal metabolism has been gradually revealed
The osteocyte lacunae sections (OLS) aspect ratio, reflecting the shape of the osteocytes, was similar in trabecular bone from Osteogenesis imperfecta (OI) type I and controls, while in cortical bone the value was increased; the lacunae were more elongated in OI type I than in controls (Figure 2, Table 1)
In trabecular and cortical bone from the same patient showed that the OLS density as well as OLS porosity were lower in trabecular bone than in cortical bone in controls and in OI
Summary
The central role of osteocytes in orchestrating skeletal metabolism has been gradually revealed. Osteocytes are the most abundant and longest-living bone cells, capable of sensing and responding to mechanical loading, secreting hormones regulating bone mineral metabolism and factors directing bone formation and resorption [1,2,3,4]. Osteocytes derive from matrix-producing polygonal osteoblasts that undergo a differentiation process, called osteocytogenesis, towards stellate cells that reside in the mineralized matrix within lacunar spaces. This transformation is characterized by a marked decrease in cell body volume and formation of multiple cytoplasmic processes running through a network of canaliculi connected to bone surface, bone marrow and blood vessels [2,3]
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