Because the pharmacokinetics of bisphosphonates suggests that they can be released from bone and re-enter the blood, there is a possibility that they can be taken up by other tissues, including muscle.
These findings suggest that in patients with metastatic bone disease, serum CTX and ICTP could reflect distinct biological pathways of bone resorption, consistent with in vitro studies showing that ICTP – but not CTX – is directly released from bone collagen matrix by MMPs, while CTX could be released from bone collagen by other proteolytic enzymes, such as cathepsin K (Garnero et al, 2003b).
In addition, gentamicin which is released from bone cement has low activity against this type of pathogens.
ICTP is released from bone type I collagen by activity of matrix metalloproteinases (MMPs), while CTX-I is generated by cathepsin K activity, but not MMPs [11].
It is released from bone matrix and is activated by osteoclastic re-absorption.
There is evidence that lead is released from bone stores, especially during increased bone turnover (Rabinowitz 1991; Silbergeld 1991).
Lead is released from bone through resorption, such as occurs with aging, and this contributes to levels found in blood (Hu et al. 1998; Smith et al. 1996).
In the process of bone remodeling, once bone resorption occurs, growth factors, e.g. IGFs and transforming growth factors (TGFs), are released from bone matrix and promote the recruitment of osteoblasts and osteoclasts to the bone surface.
In response to local and systemic injuries, including pulmonary insults, fibrocytes are released from bone marrow in higher numbers, and home to sites of injury, where they differentiate into myofibroblasts and contribute to ECM deposition [ 8, 9, 120, 121].
Mature osteoclasts secrete factors such as cardiotrophin-1, Wnt 10b, BMP-6, sphingosine-1-phosphate, and semaphorin D. 7– 9 When osteoclasts resorb bone, factors such as transforming growth factor beta, insulin-like growth factors 1 and 2, and bone morphogenetic proteins are released from bone matrix to stimulate osteoblast proliferation, differentiation and/or activity.
A concern with such a pattern of results is that it suggests that the association could be driven by reverse causation, whereby some aspect of tremor results in more bone loss and, thus, increased blood lead as lead is released from bone stores.
