Acquired Bone Disorders Flashcards
Osteoporosis
• Presentation/Screening
• Types (pathogenesis)
Patients with osteoporosis may come to attention clinically as: 1. osteopenia that results in fractures or 2. a DEXA scan with a value less than or equal to -2.5. Fractures in these patients are often seen in the vertebrae, proximal femurs, and distal radius. Fractures result from the thinning of trabeculae due to old age, reduced physical activity, genetic factors, diet (Ca2+), and hormonal factors.
Type I disease: results from LOW ESTROGEN (post-menopausal women) that causes BOTH increased osteoblastic and osteoclastic activity; however osteoclastic activity is upregulated more. This may be due to increased RANKL or less OPG or cytokines like (IL-1, IL-6, TNF)
Type II disease: results from old age which causes REDUCED OSTEOBLASTIC activity (aka low-turnover pathology).
Osteonecrosis/Avascular (Aseptic) necrosis
• what are some common causes?
• Appearance
Common causes of osteonecrosis are:
• Pancreatitis
• Fracture/Trauma
• Sickle cell disease
• Alcohol Abuse
• The Bends
• Steroids
**This is associated with WEDGE SHAPED pale areas of necrosis**
Osteomyelitis
• how is this typically contracted?
• what are symptoms of this disease?
• what should you do before initiating treatment?
Osteomyelitis in children is typically contracted by a transient bacteremia that may happen as a result of chewing vigorously or deficating. In adults this is typically contracted via fractures, surgical implantations, or cellulitis.
Symptoms: Bone pain with systemic symptoms of infection
always get blood cultures before intiating treatment
Pagets disease of bone
• Pathogenesis
• Complications
Pagets disease of bone is most often discovered incidentally on XRay and is a disease characterized by 3 phases:
1. Lytic (osteoclastic) phase
2. Mixed (osteoblastic/clastic) phase
3. Sclerotic (osteoblastic) phase
It largely affects only a single bone of the axial skeleton with lion faces and a thick skull being some defining characteristics of the disease. Because Osteoblastic activity is high we see an isolated increase in ALP. The etiology of this disease is unknown
Complications of this disease include High Output Cardiac failure as a result of AV fistula formation around bone, in rare cases the disease may progress to osteosarcoma
Osteomalacia/Rickets
- What labs do you expect to find in these diseases?
- Are any of the bone cells active during this disease process?
This patients will have low Phosphate and Low Calcium due to decreased ability to resorb Ca2+ in the Kidney, and GI tract without Vit. D.
You will have HIGH levels of ALP and HIGH PTH because lots of PTH will be secreted in response to low Ca2+ levels causing osteoblasts to become activated.
Hyperparathyroidism (primary)
• what causes this disease?
• what does this do to bone?
Primary hyperparathyroidism is caused by hyperplasia of tissue or Tumor (adenoma) of the parathyroid gland.
PTH gives osteoblasts the signal to upregulate RANK-L which leads to osteoclastic activation via RANK. Overactivation of osteoclasts ultimately leads to osteopenia.
Hyperparathyroidism (secondary)
• what causes this disease?
• What does this do to bone?
• Is PTH elevated in secondary hyperparathyroidism?
Secondary hyperparathyroidism is caused by prolonged states of hypocalcemia that result in hypersecretion of PTH.
PTH gives osteoblasts the signal to upregulate RANK-L which leads to osteoclastic activation via RANK. Overactivation of osteoclasts ultimately leads to osteopenia.
PTH levels are High in this disorder too!
Renal Osteodystrophy
• Who do we see this disease in?
• What are 5 characteristics of someone with this disorder?
Typicall Renal Osteodystrophy is seen in patients with Renal Failure that are on dialysis.
Disease Features:
1. Increased osteoclastic bone resorption mimicking osteitis fibrosa cystica
2. Osteomalacia from delayed matrix mineralization
3. Osteosclerosis
4. Growth Retardation
5. Osteoporosis
What are some treatment options for osteoporosis?
- Calcium
- Vitamin D
- Excercise - heavy resistance is more effective at increasing bone mass than light resistance
- Estrogen
- Estrogen Receptor Modulators
- Bisphosphonates
- mAbs to RANK-L
What are some common fracture sites in osteoporosis?
• which is associated with increased risk of mortality?
- Vertebrae
- Proximal Femur - increased risk of mortality (6x more likely to happen if you fall to the side
- Distal Radius
What method is typically used to Diagnose Osteoporosis?
• what labs are useful in making a diagnosis?
DEXA scans that show a value of less than -2.5 are diagnostic of osteoporosis
• Labs are NOT useful in making a diagnosis of osteoporosis because they’ll all be normal
What is the main determinant of peak bone mass?
• When do we start losing bone mass and where do we lose it from?
• How much do we lose each year?
GENETICS is the main determinant of peak bone mass
• after the age of 30 we lose ~0.7% of our bone each year. This is a loss of trabecular bone mass
What pathologic process is likely occuring here?
We see a loss of trabecular bone mass so this is probably osteoporosis on the right
What is the MOA of bisphosphonates?
• what are some important side effects of these drugs?
Bisphosphonates:
• Bind Hydroxyappetite and inhibit osteoclast activity
Side Effects:
• OSTEONECROSIS OF THE JAW (rare but important), and Erosive Esophagitis
Why do diabetics get osteomyelitis more frequently than the rest of us?
• what bug usually infects them?
• what other group of people is often infected by this bug?
pseudomonas often infects people with diabetes because these people get peripheral neuropathy and are unable to detect damage to their feet. They also have arteriolosclerosis and impaired neutrophil function .
IV drug users also get pseudomonas infections
What is happening here?
• how can you tell?
Acute Osteomyelitis
• neutrophilic infiltrate surrounded by bone gives it away
What is being pointed out by gray and yellow arrows on this picture?
What is happening here?
• what are some key features?
Osteomyelitis is shown:
• Left: Necrosis of articular cartilage
• Middle: Loss of trabeculae and Hemorrhage
• Fight: purulence
What is seen here?
What has caused the appearance of this skull?
• Describe key features of the radiograph
This is a characteristic Cotton wool appearance of the skull on radiograph. This is a feature of Paget disease.
What disease has caused this femur to appear this way?
• What would be the histologic appearance?
You can see that the cortex of this bone has become irregular and thick with replacement of normal cancellous bone with coarse thick bundles of trabecular bone
Histologically we expect to see a Mosiac Pattern from shitty bone deposition
What disease is portrayed by this histology?
• name the stain used and why the tissue appears this way.
This shows Osteomalacia/Rickets. Trabeculae are calcified and stain black with this Kossa stain while osteoid is pink. This picture shows the fact that there is a lot of osteoid deposited in rickets and osteomalacia, but it can’t be calcified.
What caused the formation of this?
This is a brown tumor that has resulted from primary or secondary hyperparathyroidism.
What are some key features of this tissue?
• what condition has lead to its formation? Explain the presence of the prominent cells.
Fibroblasts (probably recruited by TGF-beta secreted by macrophages that invaded as a result of osteoclastic bone damage) are present and are seen as spindle shaped cells throughout the tissue. Osteoclasts can be seen as the multinucleated cells present throughout.
Notice on the picture blow the presence of a resorption pit near the boney part of the tissue section where there are osteoclasts present
