The mechanism underlying the pathogenesis of osteoporosis is an imbalance
between bone resorption and bone formation (Teitelbaum 2000). The cells responsible for mineralization of bone tissue are osteoblasts, and the cells responsible for
bone resorption are osteoclasts, which inhabit the bone surface. The differentiation
of pre-osteoclasts to mature osteoclasts and the activation of these cells are regulated
by various factors belonging to the tumor necrosis factor (TNF) and TNF receptor
superfamily, including RANKL (receptor activator for nuclear factor kB ligand)
and osteoprotegerin (OPG) (Wada et al. 2006; Leibbrandt and Penninger 2008).
The RANKL/RANK interaction plays a fundamental role in the differentiation and
maintenance of osteoclast activity, and hence in the development of osteoporosis.
The discovery of the cytokine OPG has significantly contributed to the understanding
of the mechanisms controlling bone mineral density (Simonet et al. 1997). OPG
is expressed in osteoblasts and inhibits osteoclastogenesis. Hence increased levels of
this cytokine are associated with osteosclerosis (Wang et al. 2004), whereas a relative
decrease in OPG expression is linked to osteoporosis (Lane and Yao 2009).
The treatment of osteoporosis is mainly based on the use of agents that inhibit
bone resorption (Reid 2008; Canalis 2010). Current medications of osteoporosis
include the use of bisphosphonates (synthetic analogous of pyrophosphate in which
the oxygen of the P–O–P bond has been replaced by carbon; Russell et al. 1999),
selective estrogen-receptor modulators (SERMs; raloxifene; Taranta et al. 2002),
teriparatide (recombinant parathyroid hormone; Blick et al. 2009), strontium
ranelate (Ammann et al. 2004), RANKL inhibitors (Denosumab, a monoclonal
antibody mimicking OPG activity; Singer and Grauer 2010), and calcium and
vitamin D (used as nutritional supplements; Tang et al. 2007). Among the minerals,
used as supplements, silicon/silicate had attracted increasing attention since the
pioneering reports of Carlisle (1972) and Schwarz and Milne (1972).
10.2 Bone Formation
Human bone is characterized by a complex hierarchical architecture (Weiner and
Traub 1992) based on both inorganic and organic components. The inorganic matrix
of bone tissue consists of carbonated hydroxyapatite (HA) [Ca 10 (PO 4 ) 6 OH 2 ]. This
bone mineral is formed by osteoblasts which secrete alkaline phosphatase- containing
vesicles. The organic matrix of bone is mainly composed of type I collagen fibrils.
These fibrils are intimately involved in the deposition of bone mineral (see Fig. 10.6
in Sect. 10.11). Additional proteins and macromolecules (polysaccharides)
constituting the organic component of bone tissue include osteocalcin, osteonectin,
osteopontin, bone sialo protein, and glycosaminoglycans. The complex biochemical processes involved in bone formation are driven by a sophisticated network of
cytokines/growth factors, which provide, among others, the signals for the differentiation of the progenitor cells, pre-osteoblasts and pre-osteoclasts, to the mature
bone-forming cells (osteoblasts) and bone-resorbing cells (osteoclasts). The bone
morphogenic proteins (BMPs) are an important group of morphogens controlling
10 Biosilica-Based Strategies for Treatment of Osteoporosis and Other Bone Diseases
285
between bone resorption and bone formation (Teitelbaum 2000). The cells responsible for mineralization of bone tissue are osteoblasts, and the cells responsible for
bone resorption are osteoclasts, which inhabit the bone surface. The differentiation
of pre-osteoclasts to mature osteoclasts and the activation of these cells are regulated
by various factors belonging to the tumor necrosis factor (TNF) and TNF receptor
superfamily, including RANKL (receptor activator for nuclear factor kB ligand)
and osteoprotegerin (OPG) (Wada et al. 2006; Leibbrandt and Penninger 2008).
The RANKL/RANK interaction plays a fundamental role in the differentiation and
maintenance of osteoclast activity, and hence in the development of osteoporosis.
The discovery of the cytokine OPG has significantly contributed to the understanding
of the mechanisms controlling bone mineral density (Simonet et al. 1997). OPG
is expressed in osteoblasts and inhibits osteoclastogenesis. Hence increased levels of
this cytokine are associated with osteosclerosis (Wang et al. 2004), whereas a relative
decrease in OPG expression is linked to osteoporosis (Lane and Yao 2009).
The treatment of osteoporosis is mainly based on the use of agents that inhibit
bone resorption (Reid 2008; Canalis 2010). Current medications of osteoporosis
include the use of bisphosphonates (synthetic analogous of pyrophosphate in which
the oxygen of the P–O–P bond has been replaced by carbon; Russell et al. 1999),
selective estrogen-receptor modulators (SERMs; raloxifene; Taranta et al. 2002),
teriparatide (recombinant parathyroid hormone; Blick et al. 2009), strontium
ranelate (Ammann et al. 2004), RANKL inhibitors (Denosumab, a monoclonal
antibody mimicking OPG activity; Singer and Grauer 2010), and calcium and
vitamin D (used as nutritional supplements; Tang et al. 2007). Among the minerals,
used as supplements, silicon/silicate had attracted increasing attention since the
pioneering reports of Carlisle (1972) and Schwarz and Milne (1972).
10.2 Bone Formation
Human bone is characterized by a complex hierarchical architecture (Weiner and
Traub 1992) based on both inorganic and organic components. The inorganic matrix
of bone tissue consists of carbonated hydroxyapatite (HA) [Ca 10 (PO 4 ) 6 OH 2 ]. This
bone mineral is formed by osteoblasts which secrete alkaline phosphatase- containing
vesicles. The organic matrix of bone is mainly composed of type I collagen fibrils.
These fibrils are intimately involved in the deposition of bone mineral (see Fig. 10.6
in Sect. 10.11). Additional proteins and macromolecules (polysaccharides)
constituting the organic component of bone tissue include osteocalcin, osteonectin,
osteopontin, bone sialo protein, and glycosaminoglycans. The complex biochemical processes involved in bone formation are driven by a sophisticated network of
cytokines/growth factors, which provide, among others, the signals for the differentiation of the progenitor cells, pre-osteoblasts and pre-osteoclasts, to the mature
bone-forming cells (osteoblasts) and bone-resorbing cells (osteoclasts). The bone
morphogenic proteins (BMPs) are an important group of morphogens controlling
10 Biosilica-Based Strategies for Treatment of Osteoporosis and Other Bone Diseases
285