Osteocytic osteolysis: time for a second look?

Abstract

Over 100 years ago it was suggested that osteocytes could remodel their surrounding environment by removing and replacing bone. In the 1960s and 1970s, many observations were made to suggest that osteocytes could resorb bone and increase the size of their lacunae. This concept became known as osteocytic osteolysis and studies suggested that it occurred in response to diverse stimuli such as parathyroid hormone, calcium restriction, hibernation and reproductive cycles. However, this concept fell out of favor in the late 1970s when it became clear that osteoclasts were the principal bone-resorbing cells in the skeleton. Over the past decade, we have increasingly appreciated that osteocytes are remarkably versatile cells and are involved in all aspects of skeletal biology, including the response to loading, the regulation of bone turnover and the control of mineral metabolism. Recent data have demonstrated that osteocytes remodel their perilacunar and canalicular matrix and participate in the liberation of skeletal calcium stores during lactation. In light of these new findings, it may be time to reassess the concept of osteocytic osteolysis and reconsider whether osteocyte lacunar and canalicular remodeling contributes more broadly to the maintenance of skeletal and mineral homeostasis.

Hormonal Regulation of Osteocyte Perilacunar and Canalicular Remodeling in the Hyp Mouse Model of X-Linked Hypophosphatemia

“…(7) These findings suggest that PTH/PTHrP action enhances perilacunar remodeling to enable the release of calcium from the skeleton. (8) However, whether perilacunar remodeling is regulated by other mineral ion–regulating hormones such as 1,25D or FGF23 is not known. Because 1,25D or FGF23Ab treatment of Hyp mice increases serum phosphate and 1,25D while normalizing PTH, (16) the improvement in osteocyte lacunar parameters with these therapies could be due to the normalization of serum PTH, increase in serum phosphate or direct effects of these treatments on the osteocyte.…”

Intravital bone imaging by two-photon excitation microscopy to identify osteocytic osteolysis in vivo

“…Since Baud reported electron micrographic observations of osteocytes' roughly bordered lacunar walls in 1962 [6], the concept of bone resorption by osteocytes, so-called 'osteocytic osteolysis', has been proposed and reviewed [7][8][9][10][11], although these initial histological studies provided little definite evidence. On the contrary, OL enlargement has also been attributed to an artifact of specimen preparation [12]; isolated avian osteocytes fail to resorb bone in vitro [13].…”

“…These cells are 'entombed' within bone tissue, but seem to survive for extended periods, up to 25 years in humans [1]. Osteocytes are terminally differentiated osteoblasts, considered dormant until recent evidence demonstrated their critical role in endocrine regulation and bone homeostasis [2][3][4][5].Osteocytes are connected to one another via a network of cytoplasmic projections [4,5], consisting of disk-shaped osteocytic lacunae (OL) and numerous dendritic processes (canaliculi) radiating therefrom.Since Baud reported electron micrographic observations of osteocytes' roughly bordered lacunar walls in 1962 [6], the concept of bone resorption by osteocytes, so-called 'osteocytic osteolysis', has been proposed and reviewed [7][8][9][10][11], although these initial histological studies provided little definite evidence. On the contrary, OL enlargement has also been attributed to an artifact of specimen preparation [12]; isolated avian osteocytes fail to resorb bone in vitro [13].…”

Parallel mechanisms suppress cochlear bone remodeling to protect hearing

“…The extensive, interconnected lacuno-canalicular network provides osteocytes with a significant resorption surface area that is much larger than the periosteal, endosteal, and trabecular surface areas combined 7 . Thus, PLR is a powerful mechanism by which osteocytes can rapidly mobilize calcium to meet demanding metabolic conditions, such as lactation 8 . Although PLR was initially observed over a century ago 9 , known then as osteocytic osteolysis, molecular approaches have only recently been applied to understand it 2 .…”