What type of fractures do you generally see in Paget's
Chalk stick type fractures. usually in long bones.
Differentiate between intramembranous and endochondral ossification.
Endochondral ossification is developed from a hyaline cartilage template while membranous ossification is developed from a condensation of messenchymal cells that differentiate directly into osteoblasts. Woven Bone is made without a cartilage template.
What are the effects of estrogen, growth hormone, and thyroid hormones in bone formation?
GH is involved in the proliferation stage (+P). Estrogen aids in closure of growth plates (-P). T3 regulates bone mineral density and hypertrophy (+H).
What are common causes of Paget's disease of bone
Uncertain etiology. Can be genetic, environmental or viral induced.
10% of the sporadic mutations in SQSTM1 gene. leads to increased activity of NFKB
What is Technetium-99m and how is it used in the diagnosis of Mr Morales?
Isotope of a radioactive metal detectable by gamma cameras. It is a tracer for diphosphonate uptake for bone formation.
This complex gets taken up in hydroxyapatite
What are the expected lab values for Paget's disease of bone?
Serum calcium:
Serum phosphorus:
Alkaline phosphatase:
Urine hydroxyproline:
Serum calcium: No change
Serum phosphorus: No change
Alkaline phosphatase: Increase
Urine hydroxyproline: Increase
Where do these cells come from and what are their functions.
Osteocyte, Osteoblast, Osteoclast
Osteoblast: Make bone- Mesenchymal cells
Osteoclast: Bone resorption- Monocytes
Osteocyte: Mechanosensation- Osteoblasts
Why does the primary center of ossification become initially hypoxic during endochondral ossification?
There is a bone collar formation on the sides of the hyaline cartilage that is actually developed through intramembranous ossification. This will block the nutrient supply and initiate angiogenesis.
What are the stages of Paget's disease of bone?
Lytic, mixed, sclerotic, quiscent
Compared to a normal bone biopsy, what differences are expected to be seen in Mr. Morales biopsy findings?
Disorganized lines due to increased turnover. Mosaic lamellar pattern.
Dynamic bone resorption.
Bisphosphonates induce and inhibit the production of what two protein structures?
Increase osteoprotegerin release and decrease receptor activator of nuclear factor-κB ligand.
OPG is a receptor decoy for RANKL
This will decrease osteoclast activity
What is the scientific name for Paget's disease of bones
Osteitis deformans
What symptom may arise from increased temporal bone density?
Hearing loss, headaches
If osteoblasts are inhibited, what will happen to osteoclast activity?
Will also experience inhibition, osteoclasts are induced by osteoblasts.
Cortical thickening, a sign of bone fracture is seen in the CT scan. What other radiographic sign is present that leads you to differentiate the diagnosis?
Mottling of the bone is also seen which suggests increased osteoclast activity.
What is the significance of elevated serum hydroxyproline?
This is a sign of resorption. Osteoclasts release collagenase which will break down type 1 collagen.
What are potential malignancies in Paget's disease
Osteosarcoma, fibrosarcoma
Very small percentage but usually seen in polyostotic diseases.
What differential diagnosis presents with medullary inflammation
Osteomyelitis
What type of bone is seen in adult fractures and Paget's disease of bone?
Woven Bone.
Immature bone with disorganized collagen fibers.
After looking at Mr. Morales nuclear medicine images, you notice the kidneys are brightly lit. What is an possible explanation to this?
The tracer is removed by the kidneys, it is just a sign of excretion.
What is the significance of elevated alkaline phosphatase?
Enzyme released by osteoblast during the mineralization process. It is used as a marker for sclerotic activity.
Why do you think Mr. Morales is experiencing back pain?
- Spinal stenosis
- Radiculopathy
- osteoarthritis
- Abnormal bone growth can cause deformities of the lower limbs which could lead to an abnormal gait.
How can Paget's disease of bone lead to heart failure?
Bone growth would be accompanied by increased vasculature to provide the nutrients necessary. More blood vessels means the heart has to work harder to supply the bones.
Why is Zoledronic acid used if Paget's disease presents with increased cortical and medullary thickening?
It inhibits and even leads to osteoclast apoptosis. When lowering osteoclast activity you are decreasing resorption and turnover. This drug has an affinity for high turnover or high mineralized areas.
If Mr. Morales had Kidney failure, would that change any of the nuclear medicine imaging results?
The tracer is not being excreted at a normal rate and could be retained in areas that are not highly mineralized. False pasitive