vignette is diagnosed with osteoporosis. The DXA “T” score of -2 indicates
that she is four times more likely to have a spine fracture than a person with
a normal bone mineral density (BMD). The -2.5 “T” score indicates she is five
times more likely to have a hip fracture than a person with a normal BMD.
Bisphosphonate treatment is the most effective current treatment for osteo-
porosis. Bisphosphonates are analogues of the pyrophosphates and suppress
bone resorption by osteoclasts. Inhibition of osteoblastic activity (answer a)
would inhibit new bone deposition but also inhibit the production of RANK-
L (receptor for activation of nuclear factor kappa beta-ligand) and M-CSF
(macrophage colony-stimulating factor) by osteoblasts. RANK-L binds to
RANK on the osteoclast and stimulates osteoclastic activity. M-CSF stimu-
lates the differentiation of monocytes into osteoclasts. Increased RANK-L
(answer b)and M-CSF (answer c)secretion by osteoblasts and upregula-
tion of RANK (answer e)on the surface of osteoclasts will all increase osteo-
clastic activity. Some of the bisphosphonates are metabolized to a toxic
analogue that targets mitochondria and apoptosis of the osteoclasts. Others
interfere with cholesterol-dependent pathways in the osteoclast. The interac-
tions of RANK, RANK-L, and osteoprotegerin (OPG) are shown in the figure
in “High-Yield Facts” pp 20–21.
120.The answer is d.(Kumar, pp 1294–1298.)The patient in the scenario
has an osteosarcoma that has metastasized to the lungs. The osteosarcoma
cells synthesize bone and function similarly to osteoblasts, from which they
are derived. Osteoblasts and osteosarcoma cells synthesize alkaline phos-
phatase, which is critical in increasing the local calcium: phosphate ratio,
thereby inducing the calcification of osteoid (prebone) to form bone.
Osteoblasts synthesize type I collagen. Fibroblasts in highly cellular organs
such as the spleen synthesize type III collagen (answer a),the primary
component of reticular fibers. Chondrocytes in hyaline and elastic cartilage
synthesize type II collagen (answer b).Acid phosphatase (answer c)is
synthesized by osteoclasts and is essential for the dissolution of bone and
its subsequent resorption. Elastin (answer e)is synthesized by smooth-
muscle cells, endothelial and microvascular cells, chondrocytes, and
fibroblasts.
- The answer is d. (Kierszenbaum, p 997. Kumar, pp 279–281,
1294–1296. Favus, pp 372–373.)One possible target for therapy of metasta-
tic tumors, such as osteosarcoma, is to reduce metastases by upregulation of
214 Anatomy, Histology, and Cell Biology