Page 853 - Textbook of Pathology, 6th Edition

hydroxyapatite in bone and results in osteomalacia, etiology involving one (monostotic) or more bones 837
secondary hyperparathyroidism and osteitis fibrosa cystica. (polyostotic). The condition affects predominantly males over
In addition, accumulation of β -microglobulin amyloid in the age of 50 years. Though the etiology remains obscure,
2
such cases causes dialysis-related amyloidosis (page 86). following factors have been implicated:
1. There has been some evidence that osteitis deformans is a
MORPHOLOGIC FEATURES. The following skeletal form of slow-virus infection by paramyxovirus (e.g. respiratory
lesions can be identified in renal osteodystrophy: syncytial virus, measles) in osteoclasts. However, the virus
1. Mixed osteomalacia-osteitis fibrosa is the most common has not been cultured from the osteoclasts of Paget’s disease.
manifestation of renal osteodystrophy resulting from
disordered vitamin D metabolism and secondary 2. Autosomal dominant inheritance and genetic susceptibility
have been proposed on the basis of observation of 7-10 fold
hyperparathyroidism. higher prevalence of disease in first-degree relatives. The
2. Pure osteitis fibrosa results from metabolic compli- susceptibility gene located on chromosome 18q encodes for
cations of secondary hyperparathyroidism. a member of tumour necrosis factor called RANK (receptor
3. Pure osteomalacia of renal osteodystrophy is attributed activator of nuclear factor: κB).
to aluminium toxicity. Clinically, the monostotic form of the disease may remain
4. Renal rickets resembling the changes seen in children asymptomatic and the lesion is discovered incidentally or
with nutritional rickets with widened osteoid seams may on radiologic examination. Polyostotic form, however, is more
occur (page 249). widespread and may produce pain, fractures, skeletal
5. Osteosclerosis is characterised by enhanced bone deformities, and occasionally, sarcomatous transformation.
density in the upper and lower margins of vertebrae. Typically, there is marked elevation of serum alkaline
6. Metastatic calcification is seen at extraosseous sites such phosphatase and normal to high serum calcium level.
as in medium-sized blood vessels, periarticular tissues,
myocardium, eyes, lungs and gastric mucosa (page 53). MORPHOLOGIC FEATURES. Monostotic Paget’s
disease involves most frequently: tibia, pelvis, femur, skull
Skeletal Fluorosis and vertebra, while the order of involvement in polyostotic
Paget’s disease is: vertebrae, pelvis, femur, skull, sacrum
Fluorosis of bones occurs due to high sodium fluoride and tibia. Three sequential stages are identified in Paget’s CHAPTER 28
content in soil and water consumed by people in some disease:
geographic areas and is termed endemic fluorosis. Such 1. Initial osteolytic stage: This stage is characterised by
endemic regions exist in some tropical and subtropical areas of osteoclastic resorption produced by increased
areas; in India it exists in parts of Punjab and Andhra number of large osteoclasts.
Pradesh. The condition affects farmers who consume 2. Mixed osteolytic-osteoblastic stage: In this stage,
drinking water from wells. Non-endemic fluorosis results there is imbalance between osteoblastic laying down of
from occupational exposure in manufacturing industries of new bone and osteoclastic resorption so that
aluminium, magnesium, and superphosphate.
mineralisation of the newly-laid matrix lags behind,
PATHOGENESIS. In fluorosis, fluoride replaces calcium as resulting in development of characteristic mosaic pattern
the mineral in the bone and gets deposited without any or jigsaw puzzle appearance of osteoid seams or cement lines.
regulatory control. This results in heavily mineralised bones The narrow space between the trabeculae and cortex is The Musculoskeletal System
which are thicker and denser but are otherwise weak and filled with collagen which gradually becomes less
deformed (just as in osteopetrosis). In addition, there are also vascular.
deposits of fluoride in soft tissues, particularly as nodules in 3. Quiscent osteosclerotic stage: After many years,
the interosseous membrane. The patient develops skeletal excessive bone formation results so that the bone becomes
deformities and mottling of teeth. more compact and dense producing osteosclerosis.
However, newly-formed bone is poorly mineralised, soft
MORPHOLOGIC FEATURES. Grossly, the long bones and susceptible to fractures. Radiologically, this stage
and vertebrae develop nodular swellings which are produces characteristic cotton-wool appearance of the
present both inside the bones and on the surface.
affected bone.
Microscopically, these nodules are composed of heavily
mineralised irregular osteoid admixed with fluoride which TUMOUR-LIKE LESIONS OF BONE
requires confirmation chemically.
In the context of bones, several non-neoplastic conditions
PAGET’S DISEASE OF BONE (OSTEITIS DEFORMANS) resemble true neoplasms and have to be distinguished from
them clinically, radiologically and morphologically.
Paget’s disease of bone* or osteitis deformans was first Table 28.1 gives a list of such tumour-like lesions. A few
described by Sir James Paget in 1877. Paget’s disease of bone common conditions are described below.
is an osteolytic and osteosclerotic bone disease of uncertain
Fibrous Dysplasia
*It is pertinent to recall here that James Paget described Paget’s disease Fibrous dysplasia is not an uncommon tumour-like lesion
at three different anatomic sites which are not mutually interlinked in
any way: Paget’s disease of nipple (page 764), Paget’s disease of vulva of the bone. It is a benign condition, possibly of develop-
(page 722) and Paget’s disease of bone. mental origin, characterised by the presence of localised area