involved in the histogenesis of bone. A bone graft is more important as a
method of forming a temporary bridge in a severe defect than a source of
osteoprogenitor cells. Other methods useful in stimulating bone repair
include electrical forces and bone morphogenetic protein (BMP), a bone
growth factor obtained from decalcified bone matrix. BMP stimulates bone
formation when implanted at the fracture site. Pannus formation is an
inflammatory event within the synovial membrane in patients with
rheumatoid arthritis (answer d).
111.The answer is a. (Favus, pp 321–323. Kumar, pp 1284–1286.
Greenspan, pp 326–329. Kasper, pp 2279–2281.)The correct diagnosis is
Paget’s disease, also known as osteitis deformans because of its deforming
capabilities (e.g., skull or femoral head enlargement). In this disease the
serum calcium is normal, but there is an increase in osteoclastic activity
(osteolytic lesions and elevated 24-hour urine hydroxyproline) and an
increase in osteoblastic activity (elevated osteocalcin and alkaline phos-
phatase). Patients with Paget’s disease exhibit a marked increase in osteoid,
and the bone actually enlarges. The osteoid is never normally mineralized
in this disease. In this patient, the bone scan shows significant uptake of
labeled bisphosphonates, which are incorporated into newly formed
osteoid during bone formation. Her proximal femur is enlarged and no
longer fits properly into the acetabulum, which results in the hip pain.
There are a number of useful biochemical markers of bone metabolism.
Osteoclasts synthesize tartrate-resistant acid phosphatase so that increased
osteoclastic activity is reflected in increased serum levels of tartrate-resistant
acid phosphatase. Bone resorption fragments of type I collagen and noncol-
lagenous proteins increase as bone matrix is resorbed. Hydroxyproline is a
good urinary marker of bone metabolism because hydroxyproline is released
and excreted in the urine as collagen is broken down. The presence of pyridi-
noline cross-links, which are involved in the bundling of type I collagen, is
used for measurement of bone resorption. Those cross-links are released only
during degradation of mineralized collagen fibrils as occurs in bone resorp-
tion. Usually, pyridinoline cross-links are measured by immunoassay over a
24-hour period to detect excess bone resorption and collagen breakdown in
disorders such as Paget’s disease.
Markers of bone formation include osteocalcin, alkaline phosphatase,
and the extension peptides of type I collagen. Osteocalcin is a vitamin
K–dependent γ-carboxyglutamic acid protein, that is, synthesized by
210 Anatomy, Histology, and Cell Biology