Beruflich Dokumente
Kultur Dokumente
* Hyperprolactinemia * Lactation
1) Pathogenesis.
OC Synthesized by osteoblasts.
PICP and P1NP Present in bone and skin and other tissues
containing collagen.
Bone tartarate resistant acid Present in osteoclast and other macrophages. Serum
phosphatase (TRACP) level correlates with histomorphometry.
OHPr Present in all collagen molecules, released during
both bone formation and bone resorption.
Galactosy1 hydroxylysine Present only in collagen; 5/7 times more abundant in
(GHYL)* type I collagen of bone than in type 1 collagen of
skin.
Pyridinium cross-links (Pyr. & Non-reducible cross-links that form among 2
DPyr)* hydroxylysine residues on the collagen telopeptides
and one lysine or hydroxylysine residue on the α
helix protion of an adjacent molecule after deposition
of collagen in matrix DPyr is present mainly in bone.
ICTP and INTP (NTX)* Present in all tissues containing type 1 collagen
Serum IR – BSP
• Bone Sialoprotein (BSP) is a heavily glycosylated and
phosphorylated protein that accounts for 5-10% of the non-
collagenous proteins of the bone extracellular matrix. BSP
plays an important role in cell-matrix adhesion processes
and in the supramolecular organization of the extracellular
matrix of mineralized tissues.
• BSP appears to be a sensitive marker of bone turnover and
its serum levels reflects processes related to bone
resorption (Seible et al., 1996).
Evidence In Favour of A Genetic Contribution
to Osteoporosis
reliable markers.
Markers of Bone Formation
Serum biomarker Method Company Controls PMO mean Significant
Mean +SD +SD changes
CT -0.4+0.5 - -
T-score = X-M / SD
Calculated Uncoupling Status = 4.19-9.25 =
-5.06
T-Score of Biomarkers of Bone
Turnover in PMO
effects.
• RANKL and OPG are produced by bone marrow
derived stromal cells and osteoblasts and are
regulated by various calcitropic cytokinei,
hormones and drugs. Abnormalities in RANKL/OPG
ratio have been implicated in different metabolic
bone diseases characterized by increased
osteoclastic differentiation, activation and
enhanced bone resorption.
• Among the factors that increases RANKL mRNA
expression in osteoblastic cells are the
prolnflammatory cytokines IL-1, IL-6, IL-11 and
TNF-α (Yasuda et al, 1998 and Hofbauer et al,
1999). Inflammatory lesions of bone are
characterized by abundant osteoclast
proliferation.
• TNF-α is a potent osteoclastogenic agent and
appears to mediate orthopedic implant loosening
(Merkel et al, 1999). TNF-α stimulates osteoblastic
cells to express RANKL which in turn prompt
macrophages to become osteoclasts. Consistent
with this hypothesis, systemic adminstration of OPG
blocks osteoclastogenesis in experimental arthritis,
a situation in which there are abundant amounts of
TNF-α (Kong et al, 1999).
• Products of breast cancer cells (PTH rP, IL-6, IL-
11 and cyclooxygenase-2 generated prostanoids)
promote RANKL formation by acting on resident
osteoblasts and/or stromal cells (Thomas et al,
1999) The release of growth factors especially
TGFp can influence the growth of tumor cells and
their production of bone-resorbing cytokines (Vin
et al, 1999).
• Rheumatoid arthritis is characterized by destruction
of articular cartilage and by excessive subchondrial
osteoclastic bone resorption (Romas et al, 2000). In
the inflammatory state, macrophages, which
differentiate into osteoclasts, accumulate in the
rheumatoid synovial membrane where there are
many osteoclastogenic cytokines including IL, IL-6,
IL-11, IL-13, IL-17 (Kotake et al, 1999) and PTHrP.
• Rheumatoid synovial fibroblasts produce
RANKL (Romas et al. 2000) and T-cells
producing RANKL have been shown to promote
osteoclast formation without the participation of
other cells (Norwood et al, 1999).
• On the other hand OPG production is stimulated by
E2 (Saika et al, 1999), calcium cation (Yasuda et al,
1998) and bone morphogenetic protein-2 (Hofbauer
et al, 1998).
• OPG production is decreased by PGE2 (Brandstrom
et al, 1998), glucocorticoids (Vidal et al, 1998), 1α ,
25 (OH)2 D3 (Norwood et al, 1998), estrogen receptor
antagonist (Hofbauer et al, 1999) and PTH (Lee &
Lorenzo, 1999).
• Therefore RANKL/OPG, are the key agonist /
↓ E2 Hypothyroidism
↑ PRL
Decreased OPG
79: 919-924.
• Shaarawy M, Hasan M. Serum bone slaloprotein,