Bone pathology Flashcards
Achondroplasia is caused by a defect in _ gene on chromosome _
Achondroplasia is caused by a defect in FGFR3 gene on chromosome 4
Achondroplasia is caused by a [type] mutation in the fibroblast growth factor receptor, which results in _ chondrocyte proliferation and endochondral ossification
Achondroplasia is caused by a gain of function mutation in the fibroblast growth factor receptor, which results in decreased chondrocyte proliferation and endochondral ossification
* Due to the constituative activation of the FGF receptor the chondrocyte proliferation is inhibited and we see decreased longitudinal bone growth
Achondroplasia is normally [genetic pattern]
Achondroplasia is normally sporatic mutation
* Can be autosomal dominant, homozygosity is potentially fatal
* It usually occurs as a sporatic mutation but once a person has it then they pass it down in autosomal dominant fashion
_ is a known risk factor of achondroplasia
Increased paternal age is a known risk factor of achondroplasia
Achondroplasia will present with _ stature/size and [craniofacial abnormalities]
Achondroplasia will present with disproportionately short stature/size and macrocephaly, frontal bossing, flattened nose, prominent brow
Achondroplasia can cause [HEENT pathology]
Achondroplasia can cause recurrent otitis media
* Due to middle ear deformity
Achondroplasia may be associated with significant msk deformities which require surgery such as _
Achondroplasia may be associated with significant msk deformities which require surgery such as scoliosis, spinal stenosis, genu varum
* Mostly offer supportive care (physical therapy)
* Surgery as needed
* Sometimes early growth hormone therapy used
Degradation of the bone due to primary or secondary hyperparathyroidism is called _
Degradation of the bone due to primary or secondary hyperparathyroidism is called osteitis fibrosa cystica
Adenoma is a cause of [primary/secondary] hyperparathyroidism
Adenoma is a cause of primary hyperparathyroidism
* We see high calcium rather than low
Increased PTH –> _ –> activation of osteoclasts –> formation of cystic bone spaces
Increased PTH –> RANKL activation –> activation of osteoclasts –> formation of cystic bone spaces
“Brown tumors” are cystic bone spaces with _ deposition; they are caused by _
“Brown tumors” are cystic bone spaces with hemosiderin deposition; they are caused by hyperparathyroidism
* Aka osteitis fibrosa cystica
Secondary hyperparathyroidism is caused by _
Secondary hyperparathyroidism is caused by CKD
Primary hyperparathyroidism is either idiopathic, or caused by _ or _
Primary hyperparathyroidism is either idiopathic, or caused by parathyroid adenoma or malignancy
* May be paraneoplastic syndrome from carcinoma of the lung, breast, kidney, etc which secrete PTHrp
Brown tumors will present with [clinical manifestations]
Brown tumors will present with bone pain
* Additionally primary hyperparathyroidism will present with hypercalcemia- bones, stones, groans, and psychiatric overtones
The bone mineral density in osteitis fibrosa cystica will be _ ; x-ray will also reveal subperiosteal thinning, cystic lesions and a [classic skull finding]
The bone mineral density in osteitis fibrosa cystica will be decreased ; x-ray will also reveal subperiosteal thinning, cystic lesions and a salt-and-pepper skull
Serum labs in primary hyperparathyroidism:
Ca2+
PO4-
ALP
PTH
Serum labs in primary hyperparathyroidism:
Ca2+ high
PO4- low
ALP high
PTH high
Serum labs in secondary hyperparathyroidism:
Ca2+
PO4-
ALP
PTH
Serum labs in secondary hyperparathyroidism:
Ca2+ Low
PO4- High
ALP High
PTH High
Recall that in CKD there is decreased 1-a-hydroxylase (made by the kidneys) so less calcium can be absorbed in the gut; phos is high because kidneys are not excreting it appropriately
Brown tumors are treated with _ and _
Brown tumors are treated with vitamin D and addressing the underlying cause
Paget disease of bone is also called _ and it is caused by _
Paget disease of bone is also called osteitis deformans and it is caused by increased activity between RANK + RANKL –>
Increased activity of NF-kB –>
Disorganized osteoclast and osteoblast activity
Woven bone formation
Paget disease of the bone involves [bone pattern]
Paget disease of the bone involves woven bone formation
Name the (4) bone remodeling phases of paget disease
Name the (4) bone remodeling phases of paget disease
1. Lytic phase
2. Mixed lytic & blastic phase
3. Sclerotic phase
4. Quiescent stage
During the _ phase of paget disease the activity of osteoclasts and osteoblasts is down
During the quiescent phase of paget disease the activity of osteoclasts and osteoblasts is down
During the _ phase of paget disease the osteoclast activity > osteoblast leading to bone resorption
During the lytic phase of paget disease the osteoclast activity > osteoblast leading to bone resorption
During the _ phase of paget disease there is increased activity of both osteoclasts and osteoblasts such that they are working equally
During the mixed lytic and blastic phase of paget disease there is increased activity of both osteoclasts and osteoblasts such that they are working equally
* The rate of bone formation is increased compared to the lytic phase 1
During the _ phase of paget disease the activity of the osteoclasts < osteoblasts leading to increased bone formation
During the sclerotic phase of paget disease the activity of the osteoclasts < osteoblasts leading to increased bone formation
Paget disease is often an asymptomatic condition that affects [population]
Paget disease is often an asymptomatic condition that affects adults > 55 years old
* May present as bone pain, enlarging skull size, hearing impairments (compression of the nerve), or pathologic fractures
* Complications include high-output cardiac failure and osteosarcoma
Paget disease most commonly affects [bones]
Paget disease most commonly affects skull, vertebral column, pelvis, long bones
Paget disease will show the following…
X-ray:
Labs:
Paget disease will show the following…
X-ray: areas of osteolytic lesions and sclerosis
Labs: normal Ca2+, phosphorus, PTH
BUT ALP will be elevated
The only elevated lab expected in paget disease is _
The only elevated lab expected in paget disease is ALP
First line treatment of paget disease is _
First line treatment of paget disease is bisphosphonate (alendronate, risedronate, zoledronic acid)
* Alternatively can use calcitonin, vitamin D/calcium
Osteomalacia and rickets are both caused by _
Osteomalacia and rickets are both caused by vitamin D deficiency
* Without vitamin D we cannot absorb calcium in the gut
* Without calcium we can not achieve healthy osteoid mineralization
Rickets will cause [manifestations] in children
Rickets will cause impaired growth plate mineralization in children
* Leads to bony deformity like genu varum and kyphosis
* Can also have bone pain, pathologic fractures, myopathy
Children with risk factors such as _ are at increased risk of rickets
Children with risk factors such as breastfeeding, malabsorption of fat soluble vitamins, reduced UV exposure are at increased risk of rickets
X-ray of osteomalacia may reveal [findings]
X-ray of osteomalacia may reveal pseudofractures (looser zones) or osteopenia
X-ray of rickets may reveal [findings]
X-ray of rickets may reveal metaphyseal cupping/fraying, widened epiphysis, rachitic rosary, craniotabes
What serum labs are expected with osteomalacia/rickets?
Ca2+
PO3-
ALP
PTH
What serum labs are expected with osteomalacia/rickets?
Ca2+ low
PO3- low
ALP high
PTH high
Diagnosis?
Rickets- rachitic rosary (increased cartilage in kids)
Treatment of osteomalacia/rickets should include _
Treatment of osteomalacia/rickets should include vitamin D supplementation, increased Ca2+ intake
Diagnosis in this child?
Rickets- showing cupping and fraying of the metaphyses
_ is a genetic mutation of osteoclasts that results in decreased bone resorption and increased thick, poorly formed bone
Osteopetrosis is a genetic mutation of osteoclasts that results in decreased bone resorption and increased thick, poorly formed bone
Osteopetrosis is caused by a mutation in _ which impairs the osteoclasts ability to create an acidic environment (needed for bone resorption)
Osteopetrosis is caused by a mutation in carbonic anhydrase II which impairs the osteoclasts ability to create an acidic environment (needed for bone resorption)
Osteopetrosis is also called marble bone disease because of the increased risk of fracture due to _
Osteopetrosis is also called marble bone disease because of the increased risk of fracture due to thick, poorly formed bone
In addition to recurrent pathologic fractures, osteopetrosis may present with [neuro finding] or [hematologic finding]
In addition to recurrent pathologic fractures, osteopetrosis may present with cranial nerve palsies or pancytopenia
* Cranial nerve palsies due to hyperostosis of foramina
* Pancytopenia because of overgrowth of cortical bone crowding the bone marrow space- can lead to extramedullary hematopoiesis
Bone-in-bone appearance (stone bone) or symmetric dense osteosclerosis are common findings on x-ray of _
Bone-in-bone appearance (stone bone) or symmetric dense osteosclerosis are common findings on x-ray of osteopetrosis
Serum labs of osteopetrosis will show:
Ca2+
PO4-
ALP
PTH
Serum labs of osteopetrosis will show:
Ca2+ normal or low
PO4- normal
ALP normal
PTH normal
Sometimes osteopetrosis may require _ for treatment; other times _ may be sufficient
Sometimes osteopetrosis may require bone marrow transplant for treatment; other times high dose calcitriol may be sufficient
* Calcitriol is activated vitamin D which may stimulate dormant osteoclasts
Osteoporosis occurs when the activity of osteoclasts > osteoblasts leading to bone resorption and a loss of _ mass
Osteoporosis occurs when the activity of osteoclasts > osteoblasts leading to bone resorption and a loss of cortical and trabecular bone mass
Type I osteoporosis is caused by _
Type I osteoporosis is caused by low estrogen (postmenopausal osteoporosis)
Type II osteoporosis is caused by _
Type II osteoporosis is caused by age-related osteoblast decline (senile osteoporosis)
* Our osteoblasts decline as we age
Name some risk factors for osteoporosis
Name some risk factors for osteoporosis:
* Old age
* Female sex
* Smoking
* Alcohol
* Inactivity
* Poor nutrition or malabsorption (vitamin D, calcium)
Secondary causes of osteoporosis include:
Secondary causes of osteoporosis include:
* Corticosteroids
* Hyperparathyroidism
* Renal disease
* Proton pump inhibitors (decrease Ca2+ and Mg2+)
The most common fragility fractures that result from osteoporosis include _ , _ , _
The most common fragility fractures that result from osteoporosis include vertebral fractures , femoral neck , distal radius
DEXA scan with T-score _ is diagnostic for osteoporosis
DEXA scan with T-score < or equal -2.5 is diagnostic for osteoporosis
T-score -1 to 2.4 SDs on DEXA is diagnostic for _
T-score -1 to 2.4 SDs on DEXA is diagnostic for osteopenia
Pseudofractures or looser zones are commonly associated with _
Pseudofractures or looser zones are commonly associated with osteomalacia
First line pharmacologic therapy for osteoporosis is _
First line pharmacologic therapy for osteoporosis is bisphosphonates
_ is a monoclonal antibody against RANKL that can be used for osteoporosis
Denosumab is a monoclonal antibody against RANKL that can be used for osteoporosis
_ is a SERM drug that can be used for osteoporosis treatment
Raloxifene is a SERM drug that can be used for osteoporosis treatment
Adverse effects of bisphosphonates include _ , _ , and _
Adverse effects of bisphosphonates include jaw osteonecrosis , esophagitis , and hypocalcemia
Diagnosis?
Erlenmyer flask- osteopetrosis
