Acquired Disorders of Bone & Cartilage

Describe Osteoporosis

• Dif to Osteopenia

• Types

• Epi

• Bone Mass Throughout Life

• Factors → Loss (5)

• Morphology (3)

Osteoporosis 

• Osteopenia vs Osteoporosis 

  • Osteopenia  =  dec. bone mass

    • 1- 2.5 SD below mean

  • Osteoporosis = Severe Osteopenia

    • Increases fracture risk 

    • > 2.5 SD below mean

• Types:

  • Localized

  • Generalized 

    • Primary/Secondary Forms 

    • MC: senile and postmenopausal types

• Epi:

  • one million Americans experience fractures related to osteoporosis each year

• Bone Mass throughout Life

  • Young Adult = Peak bone Mass 

    • Then, Decreases 0.7%/yr

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Factors -> Loss:

• Age-Related (senile osteoporosis)

  • Osteoblasts -> 

    • reduced proliferative + biosynthetic capacity

    • Impaired response to growth factors 

• Reduced physical activity

  • Physical Activity ->  mechanical forces -> stimulates bone remodeling

    • Athletes have increased bone density

    • Resistance training + weight-bearing endurance exercise help prevent osteoporosis

• Genetic Factors:

  • Polymorphisms in:

    • RANK, RANKL

    • Osteoprotegerin (OPG)

    • Estrogen receptor

    • Vitamin D receptor

• Calcium deficiency

• Hormonal influences (postmenopausal osteoporosis)

  • Decreased Estrogen -> Increased RANKL + Decreased OPG -> Increased Osteoclast act.

  • STATS: 

    • 40% of postmenopausal women

    • Yearly reductions in bone mass may reach up to 2% of cortical bone and 9% of cancellous bone

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Morphology

• Hallmark = normal bone that is decreased in quantity

• Thinning of cortical & cancellous bone

• In postmenopausal osteoporosis

  • Vertebral Body cancellous bone particularly affected -> compression fractures

• Osteoporotic vertebral body (right) shortened by compression fractures compared with a normal vertebral body (left).

• Histologic section of normal cancellous bone. Note the interconnections between the trabeculae.

• Histologic section of bone from a case of advanced osteoporosis. The cortical bone (black arrow) is markedly thinned, and there is extensive loss of cancellous bone with a couple of trabeculae appearing as “isolated islands” of bone (blue arrows).

Epi of Paget’s

• Average age at Dx = 70 yrs

• Striking geographic variation in prevalence

• 1% of the US population > age 40 is affected

Describe Paget’s Disease (Osteitis Deformans)

• What is it

• Factors:

  • Gene (2)

  • Env. (2)

• Clinical Features (6)

• Labs (2)

• Morph of 3 phases?

What is it?

• Disorder where there is increased bone mass/turnover but disordered + structurally unsound

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Genetic factors

• 50% familial cases + 10% sporadic: SQSTM1 gene

  • Encodes p62 -> RANK signaling

    • -> NF-kB act. ->  osteoclastogenesis

• For Juvenile: LOF mutation in OPG

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Environmental Factors

• Viral infection 

  • Intranuclear inclusions (Measles?) identified in osteoclasts & precursors

• Bone marrow shown to contain paramyxovirus RNA

  • Paramyxovirus Infection -> inc. RANK expression 

• NOTE: NO live viruses have been isolated from bone

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Clinical Features

• Most = asymptomatic

• Pain Localized 

  • Polyostotic in 85%

• Skeletal System

  • Lower-Extremities Long Bones Fracture

  • VC Compression Fracture

• Leontiasis ossea

  • Enlargement of craniofacial skeleton 

• Platybasia

  • Invagination of the skull base -> Posterior Fossa Compression

• Bone Sarcoma

  • (< 1%)

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Labs:

• Increased serum alkaline phosphatase

• Normal serum calcium and phosphorus

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Morphology

• Osteolytic phase

  • Marked osteoclastic activity

  • Enlarged osteoclasts with inc. nuclei # 

  • X-rays = Lytic lesions 

• Mixed phase

  • Inc. osteoclastic/blastic act.

  • Periosseous fibrovascular tissue

  • X-Rays = Enlarged Bones 

• Osteosclerotic (quiescent) phase

  • Thick trabeculae with “mosaic” pattern

  • Little cellular activity

  • Periosseous fibrovascular tissue recedes

  • X-rays = thickened distorted bones

Histologic section of bone in the Mixed phase. The surface of the bone can be seen to be lined by osteoblasts (white arrow), as well as an osteoclast (yellow arrow). The osteoclast exhibits increased numbers of nuclei, well more than the usual 10-12 nuclei, which is typically seen in this disorder.

Left: Normal bone with cellular marrow.

Right: Histologic section of bone from patient with Paget disease in the Osteosclerotic (Quiescent) phase. The trabeculae are thickened and exhibit the so-called “mosaic” pattern, which is the histologic hallmark of Paget disease. This jigsaw puzzle-like appearance is produced by unusually prominent cement lines, which join haphazardly oriented units of lamellar bone. There is little or no detectable osteoclastic or osteoblastic activity, hence the term “quiescent” for this phase.

Describe Rickets

• Dif. to Osteomalacia

• Causes (4)

• Clinical Features (3) (4)

• Morphology (6)

Dif. to Osteomalacia:

• Osteomalacia:

  • Adult Disorder

  • Inadequate Bone mineralization 

• Rickets:

  • Child Disorder

  • Inadequate Bone mineralization  + cartilaginous growth plate

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Causes:

• Dietary deficiency of vitamin D

• Disorders of vitamin D metabolism

• Inadequate exposure to sunlight

• Malabsorptive disorders

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Clinical Features

• Loss of Rigidity -> Skeletal deformities:

  • Frontal bossing

  • Leg Bowing

  • Rachitic rosary

  • Pectus carinatum (pigeon breast)

• Shortened limbs

• Frequent fractures

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Morphology

• Excess  of Unmineralized bone matrix 

• Growth plate abnormalities:

  • Mineralization Zone inadequately mineralized

  • Osteoclasts do not resorb poorly mineralized cartilage

  • Growth plate cartilage continues growing 

    • marked thickening of growth plate

  • Proliferating cartilage extend -> metaphyseal region

  • Only minimal amount of primary spongiosum is formed

Left: Frontal bossing

Right: Rachitic rosary

Left: Pectus carinatum (pigeon breast). Pectus carinatum is also known as “pigeon chest.”

Right: Toddler exhibiting “bowing” of the legs.