Calcium and Phosphorus
TABLE 37-3
Biochemical Markers o f Bone Formation and Bone Resorption
Markers of Bone Formation (measured in serum)
1. B on e-sp ecific alkaline phosphatase: R ich in osteoblasts
2. O steocalcin: M ajor noncollagen protein o f bone matrix
3. A m ino- and carboxyl-term inal Procollagen 1 extension peptides:
By-product o f collagen biosynthesis
Markers of Bone Resorption
Serum marker
B on e sp ecific acid phosphatase: A lysosom al en zym e o f osteoclasts
Urine Markers: A ll o f these are collagen breakdown products
1. N -T elopeptide and C -T elopeptide
2. Pyridinium cross-links (pyridinoline and deoxypyridinoline):
Posttranslational m odification o f lysine and hydroxylysine
residues o f collagen
3. H ydroxlysine glycosid es
4. H ydroxyproline
is greater than bone form ation. R ecent research indicates
that peak bone m ass, skeletal structure, and m etabolic
activity are determ ined by a large num ber o f different
gen es interacting w ith environm ental factors; thus, o s-
teoporosis is a polygenic-m ultifactorial disease. C andi-
date gen es that m ay play a role in the developm ent o f
osteoporosis include vitam in D receptor, estrogen recep-
tor, transform ing growth factor
interleukin-6, colla-
gen type 1 gen es, and collagenase. G ene knockout m ice
are used in assessin g the contribution o f various genes
to bone form ation and bone resorption. K nockout o f the
hem opoietic transcription factor PU -1 in m ice results in
the phenotype o f osteoporosis; these m ice are character-
ized by d efective osteoclast form ation and deficiency o f
m acrophages. K nockout o f the m yeloid growth factor (M -
C SF) gene produces a sim ilar phenotype. H ow ever, knock-
out o f the transcription factor c
gene causes osteopet-
rosis w ith normal m acrophage synthesis w hile knockout
o f the transcription factor
allow s form ation o f o s-
teoclasts that are unable to resorb bone norm ally. D efi-
cien cies o f other m olecules, such as cathepsin K, carbonic
anhydrase II, and tartrate-resistant acid phosphatase, also
im pair the ability o f mature osteoclasts to resorb bone.
It is apparent that many factors influence developm ent o f
O steoporosis is a com m on diagnosis in postm enopausal
w om en. M enopause results from the perm anent cessa-
tion o f ovarian function that usually precedes the final
m enses by several years and is diagnosed after 12 m onths
o f amenorrhea. M enopause and osteoporosis are causally
related based on (a) the higher rates o f osteoporotic
fractures in postm enopausal w om en; (b) loss o f bone
m ineral density in postm enopausal w om en; and (3) preser-
vation o f bone m ineral density
a result o f hor-
m one replacem ent therapy. M ost studies o f horm one
replacem ent therapy involving estrogen or estrogen plus
progestagen show ed increases in bone m ineral density o f
1-4% in postm enopausal w om en. A lthough the increase in
bone density is sm all, significant reduction in fractures is
reported for w om en using horm one replacem ent therapy.
Estrogen or other drugs are used to prevent osteoporo-
sis in postm enopausal w om en. B isphosphonates and cal-
citonin act as antiresorptive drugs. A ctually, these drugs
decrease the rates o f both bone resorption and bone for-
m ation, but they affect the rem odeling cy cle so that there
is a net increase in bone m ineral density o f 5-10% . Both
etidronate and alendronate (bisphosphonates, Figure 37-6)
o f osteoporosis
m enopausal w om en and provide a treatment option if es-
trogen replacem ent therapy is contraindicated. It is thought
that bisphosphonates are incorporated into bone matrix
and incapacitate osteoclasts upon entry during resorption.
Prom otion o f osteoclast apoptosis through inhibition o f the
m evalonate-cholesterol biosynthetic pathway, w hich leads
to loss o f G-protein prénylation, is also a p ossib le m echa-
nism o f action. The use o f H M G -C oA reductase inhibitors
(statins), w hich also inhibits G -protein prénylation, d e-
creases the risk o f fractures in the elderly (discussed ear-
lier). Statins, independent o f their lipid-low ering activity,
can im prove endothelial function including the form ation
previous page 922 Bhagavan Medical Biochemistry 2001 read online next page 924 Bhagavan Medical Biochemistry 2001 read online Home Toggle text on/off