MS - Path (Bone disorders) Flashcards
Pg. 419-421 in First Aid 2014 Sections include: -Achondroplasia -Osteoporosis -Osteoporosis (marble bone disease) -Osteomalacia/rickets -Paget disease of bone (osteitis deformans) -Osteonecrosis (avascular necrosis) -Lab values in bone disorders
What is achondroplasia? What physical traits are versus are not affected, and why/why not?
Failure of longitudinal bone growth (endochondral ossification) => short limbs. Membranous ossification is not affected => large head relative to limbs
What is the molecular defect in achondroplasia, and what impact does that have?
Constitutive action of fibroblast growth factor receptor (FGFR3) actually inhibits chondrocyte proliferation.
What percentage of mutations leading to achondroplasia occur spontaneously, and with what condition are such mutations associated? Otherwise, what mode of inheritance does Achondroplasia exhibit?
> 85% of mutations occur sporadically and are associated with advanced paternal age, but the condition also demonstrates autosomal dominant inheritance.
Of what condition is Achondroplasia a common cause?
Common cause of dwarfism
How does Achondroplasia affect life span and fertility?
Normal life span and fertility.
In general, what bone and lab findings define osteoporosis?
Trabecular (spongy) bone loss mass and interconnections despite normal bone mineralization and lab values (serum Ca2+ and [PO4]3-)
How is osteoporosis diagnosed?
Diagnosed by a bone mineral density test (DEXA) with a T-score of < or = -2.5
What habit can cause osteoporosis?
Can be caused by long-term exogenous steroid use
What musculoskeletal complication can result from osteoporosis? What are 3 signs/symptoms of this condition?
Can lead to Vertebral crush fractures - acute back pain, loss of height, kyphosis
What are the types of osteoporosis?
Type I (Postmenopausal) & Type II (Senile osteoporosis)
What is the mechanism behind Type I osteoporosis?
Postmenopausal: Increased bone resorption due to decreased estrogen levels
What patient populations does Type II osteoporosis affect?
Senile osteoporosis: Affects men and women > 70 years old
What 2 fractures are associated with Type I (Postmenopausal) osteoporosis?
(1) Femoral neck fracture, (2) Distal radius (Colles) fracture
What is the prophylaxis for Type II (Senile) osteoporosis?
Prophylaxis: Regular weight-bearing exercise and adequate calcium and vitamin D intake throughout adulthood
What are 5 treatments for Type II (Senile) osteoporosis?
Treatment: (1) Bisphosphonates (2) PTH (3) SERMs (4) Rarely calcitonin; (5) Denosumab (monoclonal antibody against RANKL)
What is Denosumab? For what specific condition is it used as treatment?
Denosumab (monoclonal antibody against RANKL); Type II (senile) Osteoporosis
What is another name for Osteopetrosis?
Osteopetrosis (Marble bone disease)
What is the defect in Osteopetrosis, and what effect(s) does it have on the bone?
Failure of normal bone resorption due to defective osteoclasts => thickened, dense bones that are prone to fracture
What hematologic effect does osteopetrosis have, and why?
Bone fills marrow space => pancytopenia, extramedullary hematopoiesis.
What phenotypic effect do mutations related to osteopetrosis have? Give an example of such a mutation.
Mutations (e.g., carbonic anhydrase II) impair ability of osteoclast to generate acidic environment necessary for bone resorption
How does osteopetrosis appear on x-ray?
X-rays show show bone-in-bone appearance
What complications can result from osteopetrosis, and why?
Can result in cranial nerve impingement and palsies as a result of narrowed foramina
What is a potential cure for Osteopetrosis, and why?
Bone marrow transplant is potentially curative as osteoclasts are derived from monocytes
What deficiency causes Osteomalacia/Rickets? In which patient population is each of these conditions seen?
Vitamin D deficiency; Osteomalacia in adults, Rickets in children
Explain the pathophysiology of Osteomalacia/rickets as it relates to the gross appearance of bone in these patients.
Due to defective mineralization/calcification of osteoid => soft bones that bow out.
Explain the pathophysiology of Osteomalacia/rickets as it relates to the lab findings in these patients.
Low vitamin D => low serum calcium => high PTH secretion => low serum phosphate. Hyperactivity of osteoblasts => high ALP (osteoblasts require alkaline environment)
What is another name for Paget disease of the bone?
Paget disease of bone (osteitis deformans)
Is Paget disease of bone common? What kind of disorder is it, and what causes it?
Common, localized disorder of bone remodeling caused by increase in both osteoblastic and osteoclastic activity
What are the lab findings associated with Paget disease of bone?
Serum Ca2+, phosphorus, and PTH levels are normal. High ALP.
What histology characterizes Paget disease of bone?
Mosaic pattern of woven and lamellar bone
What kind of fractures characterize Paget disease of bone?
Long bone chalk-stick fractures
What cardiologic complication may result from Paget disease of bone, and why?
Increased blood from increased arteriovenous shunts may cause high-output heart failure
What risk is increased with Paget disease of bone?
Increased risk of osteogenic sarcoma
What 2 physical exam findings characterize Paget disease?
(1) Hat size can be increased (note marked thickening of calvarium) (2) Hearing loss is common due to auditory foramen narrowing
What are the stages of Paget disease, and what cell(s) act(s) during each?
Stages of Paget disease: (1) Lytic - osteoclasts (2) Mixed - osteoclasts + osteoblasts (3) Sclerotic - osteoblasts (4) Quiescent - minimal osteoclast/osteoblast activity
What imaging finding may indicate Paget disease of bone?
marked thickening of calvarium
Why is hearing loss common in Paget disease?
Hearing loss is common due to auditory foramen narrowing
What is another name for Osteonecrosis?
Osteonecrosis (avascular necrosis)
What is Osteonecrosis? In general, how does it present?
Infarction of bone and marrow, usually very painful
What are 4 causes of Osteonecrosis (avascular necrosis)?
Caused by trauma, high-dose corticosteroids, alcoholism, sickle cell.
What is the most common site of Osteonecrosis (avascular necrosis), and why?
Most common site is femoral head (due to insufficiency of medial circumflex femoral artery).
What change does Osteoporosis cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?
(1) No change (2) No change (3) No change (4) No change
What change does Osteopetrosis cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?
(1) No change/Decrease (2) No change (3) No change (4) No change
What change does Paget disease cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?
(1) No change (2) No change (3) Increase (4) No change
What change does Osteomalacia/Rickets cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?
(1) Decrease (2) Decrease (3) Increase (4) Increase
What bone description characterizes each of the following: (1) Osteoporosis (2) Osteopetrosi s (3) Paget disease (4) Osteomalacia/Rickets?
(1) Low bone mass (2) Dense, brittle bones (3) Abnormal “mosaic” bone architecture (4) Soft bones
In what ways can Osteopetrosis affect Ca2+ levels, and in what context(s)?
Normal or low serum Ca2+; Ca2+ decreased in severe, malignant disease
What change does Hypervitaminosis D cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?
(1) Increase (2) Increase (3) No change (4) Decrease
What are 2 causes of Hypervitaminosis D?
Caused by over-supplementation or granulomatous disease (e.g., sarcoidosis)
What are the 2 types of osteitis fibrosa cystica? What change does each cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?
PRIMARY HYPERPARATHYROIDISM: (1) High (2) Low (3) High (4) High; SECONDARY HYPERPARATHYROIDISM: (1) Low (2) High (3) High (4) High
What physical finding characterizes osteitis fibrosa cystica, and what causes this?
“Brown tumors” due to fibrous replacement of bone, subperiosteal thinning
What are 4 potential causes of primary hyperparathyroidism?
Idiopathic or parathyroid hyperplasia, adenoma, carcinoma
In what context does secondary hyperparathyroidism often occur, and why?
Often as compensation for ESRD (low [PO4]3- excretion and production of activated vitamin D)
