Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrinology > Calcium/Bone > Flashcards

Calcium/Bone Flashcards

1
Q

FGF-23:

  1. What is it? What causes its release?
  2. MOA?
A
  1. a phosphaturic hormone made by osteocytes. Elevated phosphate, 1,25OH2D, vitamin D, and PTH increases FGF23 release
  2. decreases proximal tubule phosphate reabsorption, stimulates 24-hydroxylase release, inhibits 1-alpha-hydroxylase –> inhibiting PTH synthesis and secretion by the parathyroid glands
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

X-linked hypophosphatemia (XLH):

  1. affected gene?
  2. MOA?
  3. treatment?
A
  1. PHEX
  2. increases FGF23 –> low phosphate, normal/low 1,25OH2D (d/t decreased 1-alpha-hydroxylase expression and increased breakdown of 1,25OH2D)
  3. phosphate and calcitriol;
    BUROSUMAB (a monoclonal Ab to FGF-23) for those who cannot achieve good control on conventional therapy
    -relatively unresponsive to vitamin D
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what alternative medication is FDA approved to treat hypercalcemia of malignancy that is refractory to bisphosphonate therapy? MOA?

A

Denosumab
MOA: monoclonal Ab to receptor-activated nuclear factor kappa-B ligand (RANKL) –> reduces osteoclast formation, function, and survival –> decreased bone resorption (and also formation)
Make sure to give patients vitamin D d/t higher risk of hypocalcemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are contraindications to the use of teriparatide?

A

history of skeletal irradiation
Paget disease of the bone
unexplained elevation of alk phos
(think twice in patients with h/o kidney stones as it can cause hypercalciuria)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Paget’s disease: indications for treatment in asymptomatic patients (5).
TX?

A
  1. involvement of:
    a. weight-bearing bone (eg, spine, leg)
    b. near a joint
    c. skull
  2. serum alk phos > 3x ULN
  3. before orthopedic surgery (large joint replacement in close proximity to a pagetic lesion)

TX: ZOLEDRONIC ACID - normalizes bone turnover markers and maintains normal values for the longest duration of any medication

pathophysiology: abnormal osteoclasts –> increased bone resorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

The 2017 guidelines from the American College of Rheumatology recommend pharmacologic tx for adults 40+ yrs with a moderate fracture risk, defined as?

A

a glucocorticoid-adjusted FRAX risk of 10-19% for major osteoporotic fracture or 1.1-2.9% for hip fracture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Calcium emergency: hypocalcemia

Initial and subsequent treatments include (bolus + infusion)?

A
  1. IV bolus of calcium GLUCONATE - 150 mg
    +
    continuous calcium gluconate infusion of 1 mg/kg per h
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Patients at moderate or high 10-year risk for a major osteoporotic fracture taking at least how much pred?

A

2.5 mg of prednisone daily for 3 months or more should begin prophylactic bisphosphonate therapy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

In chronic hypoparathyroidism, the goals of therapy are to eliminate symptoms while avoiding complications of therapy; monitoring what is mandatory?

A

urine calcium excretion is mandatory because hypercalciuria often limits therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the appropriate therapy in a patient with low bone density and prostate cancer on androgen-deprivation therapy? AE?

A

denosumab (FDA approved, unlike bisphosphonates)
AE: hypocalcemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

In patients with PTH-mediated hypercalcemia, age less than 40 years, and 24-hr urinary calcium-to-creatinine ratio between 0.01 and 0.02, what should typically be pursued?

A

genetic confirmation (to detect FHH due to clinically significant CASR variants)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

After completion of a 5-year course of alendronate therapy, what major osteoporotic fracture risk score would confer continuation of therapy?

A

> 23% and also in those who remain osteoporotic at the femoral neck.

*Do not use teriparatide after long-term bisphosphonate therapy since its effect on BMD is blunted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Raloxifene can reduce the risk of [ ] fracture?
CI in its use?

A

vertebral, but not hip or nonvertebral
CI: increased risk of VTE - smoker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

for a postmenopausal woman with severe osteoporosis, what is the best initial treatment?

A

romosozumab
can be followed by denosumab
(as demonstrated in the FRAME study - Fracture Study in Postmenopausal Women With Osteoporosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Romosozumab:
1. MOA?
2. contraindication?

A
  1. binds sclerostin; has both anabolic and antiresorptive effects
  2. do not initiate in patients who have had an MI or stroke within the last year
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

In a patient with primary hyperparathyroidism secondary to long-term lithium use, what is recommended to effect the greatest likelihood of long-term cure?

A

refer to endocrine surgery for bilateral neck exploration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

cinacalcet
1. MOA?
2. indications for use?
3. when is immediate treatment with SQ calcitonin or IV bisphosphonate indicated?

A
  1. A calcimimetic. Activates the calcium-sensing receptor in the parathyroid gland –> inhibits PTH secretion
  2. to lower serum calcium and increasing serum phosphate in patients with primary hyperparathyroidism, but are unable to undergo parathyroidectomy
  3. acute severe hypercalcemia (albumin-corrected calcium > 14 mg/dl)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

In chronic hep B, what medication can cause hypophosphatemic osteomalacia and hip fracture?

A

tenofovir (stop if possible)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

osteogenesis imperfecta
-characterized by?
-Types of OI (I to V) - mild, severe, severe, mod, mod
-treatment?

A
  • fragile bones with recurrent fractures
    -Type I (mild): blue sclerae, hearing loss in 50%, normal lifespan
    -Type II (severe): perinatal form, death in 1st year of life
    -Type III (severe): many fractures ealry in life (wheelchair), shortened lifespan
    -Type IV (moderate): braces or crutches to walk; normal lifespan
    -Type V (moderate): no blue sclera, hyperplastic callus, forearm calcification, osteoporosis

Treatment: bisphosphonates IV preferred –> leads to increased bone mineral density in adults.
In children, decreased bone pain and fracture risk.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Hereditary resistance to vitamin D:
1. caused by?
2. gene affected?
3. lab findings?

A
  1. end-organ resistance to 1,25-dihydroxyvitamin D
  2. loss-of-function pathogenic variants in Vitamin D receptor (VDR) gene
  3. hypocalcemia, hypophosphatemia, high PTH, high 1,25-dihydroxy D
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Transient osteoporosis of the hip:
1. clinical presentation?
2. finding on MRI
3. treatment?

A
  1. subacute, intense discomfort in the hip, exacerbated by weight bearing
  2. diffuse edema of the femoral head and neck (different from crescent sign in avascular necrosis)
  3. bisphosphonates (oral or IV) to shorten recovery time, rest, restricted weight bearing, analgesics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q
  1. Osteopenia + low-trauma fracture at [what sites?] = [ ? ]
  2. A fragility fracture outside of these sites in a patient with osteopenia by bone density measurement should prompt use of? When is pharmacologic osteoporosis therapy recommended?
A
  1. sites: vertebral, hip, pelvis, proximal humerus, distal forearm
    = osteoporosis
  2. The FRAX calculator.
    A T score of -1 to -2.5 and a 10 year probability of 20% or higher for major osteoporotic fractures or 3% or higher for hip fractures
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

McCune-Albright syndrome (aka fibrous dysplasia):

  1. associated with?
  2. biochemical findings?
  3. clinical characteristics?
  4. Gene involved?
  5. classic humeral shaft lesion?
A
  1. rickets and osteomalacia, precocious puberty
  2. hyperphosphaturic hypophosphatemia
  3. polyostotic fibrous dysplasia, cafe-au-lait macules (mimicking the coast of Maine), other endocrine disorders (thyrotoxicosis, acromegaly, Cushing).
  • precocious puberty in females
  • macro-orchidism in males
  1. germline mutation of GNAS (NOT inherited; encodes the alpha subunit of the stimulatory G protein)
  2. “ground glass” appearance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Albright Hereditary Osteodystrophy
1. associated with what conditions?
2. clinical characteristics
3. labs?
4. gene involved

A
  1. pseudohypoparathyroidism or pseudopseudohypoparathyroidism due to end organ resistance to PTH thus resulting in hypocalcemia
  2. brachydactyly (shortening of the 3rd, 4th, and 5th metacarpals), round facies, short stature, obesity, developmental delay, and subcutaneous calcifications
  3. HIGH PTH and phos; LOW calcium
    Labs are normal in pseudopseudo- (paternally transmitted)
  4. loss of function of GNAS (alpha subunit of G protein, which is linked to the PTH receptor); other resistance to various G-protein coupled hormones include TSH, LH, FSH, and GnRH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

In a patient with chronic hypoparathyroidism who is at risk for kidney complications, what routine monitoring is recommended?

A

24-hour urinary calcium excretion every 1-2 years and kidney imaging (US > CT) at baseline and Q5 years if asx, and more frequently if +sx’s.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

In a patient with chronic hypoparathyroidism who is at risk for kidney complications, what routine monitoring is recommended?

A

24-hour urinary calcium excretion every 1-2 years and kidney imaging (US > CT) at baseline and Q5 years if asx, and more frequently if +sx’s.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the three types of FHH (familial hypocalciuric hypercalcemia)?

A

type 1. pathogenic variants in the calcium-sensing receptor gene (CASR)

type 2. pathogenic variants in the guanine nucleotide-binding G-protein subunit alpha11 gene (GNA11)

type 3. pathogenic variants in the adaptor-related protein complex 2, sigma 1 subunit gene (AP2S1)

“Family, Casper and Gina went ape shit”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Management of severe, acute hypocalcemia

A

IV bolus of 150 mg calcium GLUConate then continuous calcium gluconate infusion of 1 mg/kg/hr

29
Q

What are the recommendations for management of low bone mass in patients with breast cancer on aromatase inhibitor?

A

Start an antiresorptive treatment (IV zoledronic acid) when pt starts AI, and for the duration of AI treatment.
This applies to both pre- and postmenopausal women

30
Q

Hypophosphatasia:

  1. clinical features?
  2. lab findings?
  3. what gene is involved?
  4. treatment for infantile and childhood onset? what medication needs to be avoided?
A
  1. low bone mineral density with or without fragility fractures, abnormal dental mineralization with excessive primary tooth loss
    • affected adults most commonly present with stress fractures of the lower extremities (metatarsal, proximal femur)
  2. LOW alkaline phosphatase; HIGH serum pyridoxal 5’-phosphate
  3. ALPL (or TNSALP gene)
  4. asfotase alfa
    1. AVOID bisphosphonates as they can worsen osteomalacia
31
Q

How do you definitively diagnose renal bone disease/osteodystrophy

A

tetracycline-labeled iliac crest bone biopsy

(low 25OHD, high PTH, low bone density are consistent with osteitis fibrosa cystica and osteomalacia)

32
Q

Carney complex
1. characteristics
2. gene involved

A
  1. a rare, multiple endocrine neoplasia syndrome; lentiginous pigmented lesions of the skin and mucosa (perioral and mucosal freckling), cardiac and noncardiac myxomas, thyroid nodules
  2. PRKAR1A (inactivating pathogenic variants in the protein kinase A type I alpha regulatory subunit gene). A.D.
33
Q

Neurofibromatosis type 1
1. gene involved
2. characteristics?
3. mode of inheritance

A
  1. NF1 tumor suppressor gene (inactivating pathogenic variants, which encodes the protein neurofibromin)
  2. aka von Recklinghusen disease
    multiple cafe-au-lait macules and neurofibromas (“coast of California”), iris hamartomas (Lisch nodules), optic pathway gliomas, GIST, bone abnormalities
  3. autosomal dominant
34
Q

von Hippel-Lindau disease
1. gene involved
2. clinical manifestations

A
  1. VHL tumor suppressor gene
  2. hemangioblastomas, pheochromocytomas, renal cell carcinomas, pancreatic tumors, endolymphatic sac tumors of the middle ear, papillary cystadenomas of the epididydmis and broad ligament
35
Q

X-linked hypophosphatemic rickets:

  1. mode of inheritance?
  2. defective gene?
  3. Lab findings?
  4. Treatment?
A
  1. X-linked dominant
  2. PHEX
  3. high FGF23, low phos (with inappropriately normal 1,25-dihydroxy D)
  4. Burosumab
36
Q
  1. What radiographic finding is characteristic of osteomalacia?
  2. What are biochemical clues to osteomalacia?
A

1.** looser zone or pseudofractures** (transverse zones of rarefraction)
2. very low vitamin 25OHD (< 10 ng/ml), hypocalcemia, hypophosphatemia, high PTH, and elevated alkaline phosphatase

37
Q

contraindications to using raloxifene

A

(from the RUTH trial)
a higher risk for fatal stroke in women with HTN, DM, Afib. Also smoker

38
Q

What is this picture suggestive of?

A

Impending fracture seen with atypical femoral fractures.
X-ray shows areas of lateral cortical thickening that cause a “beaking” or “flaring”.

If a patient on a bisphosphonate therapy reports persistent thigh or groin pain, get an xr of the affected hip.
Tx = prophylactic reconstruction nail fixation

39
Q

what lab findings are seen in homozygous CYP24A1 mutations?

A

inappropriately low 24,25-dihydroxyvitamin level

  • seen in adults presenting with kidney stones or noted in idiopathic infantile hypercalcemia
  • PTH is undetectable
  • 1,25-dihydroxyvitamin D is inappropriately high (should be low since PTH is low)
40
Q
  1. a urinary calcium-to-creatinine ratio <0.01 is consistent with a diagnosis of?
  2. what is the caveat?
  3. A patient with no identifiable CASR pathogenic variants and clinical concern for FHH should be tested for?
A
  1. FHH
  2. patients must be vitamin D replete ( >20 ng/ml) with good renal function for the collection to be interpretable
  3. GNA11 and AP2S1 genetic testing

(a family of Gina and apes)

41
Q

TRUE or FALSE

In primary hyperparathyroidism, PTH facilitates the conversion of 25-OHD to 1,25-dihydroxyvitamin D, and up to 25% of patients have frankly elevated 1,25-dihydroxyvitamin D levels

A

TRUE

42
Q

in what conditions would PTH expected to be suppressed?

A

granulomatous disease, calcitriol toxicity, humoral hypercalcemia of malignancy

43
Q

What percentages are considered to be the least significant change in the following sites in clinical DXA studies?

  1. total hip
  2. femoral neck
A
  1. 2.8%
  2. 5%
44
Q

teriparatide is contraindicated in a patient who has received prior?

A

irradiation therapy

45
Q

TRUE or FALSE: Vertebral fractures are strong independent predictors of both future vertebral and nonvertebral fractures

A

TRUE an acute vertebral compression fracture warrants intervention with antiresorptive therapy regardless of the DXA results

46
Q

adynamic bone disease, a type of renal osteodystrophy (now called chronic kidney disease-mineral bone density disorder or CKD-MBD):
1. is present in at least 1/3 of?
2. classic presentation
3. lab findings

A
  1. patients receiving dialysis
  2. multiple fragility fractures due to very low bone turnover, reduced osteoclast and osteoblast activity, no accumulation of osteoid, and high fracture risk
  3. very low alk phos, PTH relatively low (less than 150)
47
Q

Case: 60 yo man with muscle and bone pain, fatigue, weakness, spontaneous fractures, and difficulty walking, low DXA scores. 1. what to measure? 2. common biochemical finding?

A
  1. FGF23. It causes renal tubular loss of phosphate and inhibits 1alpha-hydroxylase (and low 1,25-dihydroxy vitamin D)
  2. low 1,25-dihydroxyvitamin D levels
48
Q

In patients with pathogenic variants in the CYP24A1 gene (a rare cause of non PTH-mediated hypercalcemia), what are the common findings (3)?

A

LOW 24,25-dihydroxyvitamin D, hypercalcemia, and kidney stones, elevated 1,25-dihydroxyvitamin D

49
Q
  1. If a patient has Paget disease, what is the next imaging modality to use?
  2. For Paget disease, what are the classic biochemical findings?
  3. If a patient has multiple myeloma, what is the next imaging modality to use?
A
  1. bone scan
  2. Elevated ALK PHOS and elevated Urinary N-telopeptide
  3. skeletal survey
50
Q
  1. In patients with multiple stone episodes who have already increased their fluid intake, what is the best treatment?
  2. the goal is to aim for urine volume greater than?
A

1) HCTZ (enhances renal calcium reabsorption to reduce urinary calcium excretion), citrate supplements (citrate acts as a stone inhibitor)
2) 2.5 L per day

51
Q

In young patients < 30 yo who present with primary hyperparathyroidism, what do you screen for?

A

MEN1 pathogenic variants -hereditary syndromes should be suspected in anyone with a personal history of other endocrine tumors (especially pancreatic or pituitary) or a family history of parathyroid disease -others include: MEN2, MEN4, and hyperparathyroidism-jaw tumor syndrome

52
Q

What diabetes medications are associated with increased fracture risk in patients with type 2 diabetes?

A

pioglitazone and canagliflozin

53
Q

Within the first 6 months after liver transplant, what happens to BMD?

A

there is a significant decline in bone mineral density. The high-turnover state documented after liver transplant is thought to be due to a combination of factors, including resolution of the liver disease, use of glucocorticoid therapy, and the development of secondary hyperparathyroidism due to possible renal effects of the immunosuppressant therapy. This is in contrast to the decreased bone formation and low turnover typically seen before liver transplant.

54
Q

A number of studies have shown that patients who are overweight or obese require much [?] dosages of vitamin D than normal-weight participants to achieve adequate levels

A

higher Obese patients are estimated to require 2 to 3 times the usual daily dose of cholecalciferol to achieve adequate levels. The mechanism is not well understood.

55
Q

The most consistent benefit of bisphosphonate therapy in affected adults with osteogenesis imperfecta (COL1A1/COL1A2) is?

A

increased bone mineral density

56
Q

In a patient with elevated PTH despite normal 25-OH vitamin D and serum calcium levels, what should be suspected?

A

calcium deficiency. Therefore, measure 24-hour urinary calcium excretion.

57
Q

Vitamin-D resistant rickets:

  1. characteristics?
  2. What is the key to distinguishing vitamin D-resistant rickets from other forms of rickets?
  3. In true vitamin D-DEFICIENT (not resistant) rickets, what level is 25-hydroxyvitamin D?
A
  1. low serum calcium, low serum phosphate, HIGH PTH, normal 25-hydroxyvitamin D levels
  2. measure 1,25 dihydroxyvitamin D: can be LOW or UNDETECTABLE in pathogenic variant in the gene encoding 1alpha-hydroxylase enzyme, but HIGH in the gene encoding the vitamin D receptor (aka true vitamin D-resistant rickets)
  3. too low to be measured
58
Q

Oncogenic osteomalacia: Lab findings?

A

Very low 1,25-dihydroxyvitamin D due to suppression by FGF23 (which is HIGH)

59
Q

autoimmune polyendocrine syndrome type 1:

clinical features?

A

need 2 out of the 3 of the following: -primary hypoparathyroidism -chronic mucocutaneous candidiasis -autoimmune adrenal insufficiency

60
Q

autoimmune polyendocrine syndrome type 2:

clinical features?

A

Addison disease + either T1DM or autoimmune thyroid failure, or both

61
Q

autoimmune polyendocrine syndrome type 3:

clinical features?

A

autoimmune thyroid disease and autoimmune disorders other than Addison disease or hypoparathyroidism More common: nonendocrine autoimmune diseases - Sjogren syndrome, alopecia areata

62
Q

A rare complication of Paget disease is?

A

the transformation of the pagetoid bone into malignant osteosarcoma.

*Sarcoma should be suspected when new pain and swelling develop in a previously affected bone

63
Q

Treatment with recombinant human PTH 1-34 (teriparatide), an anabolic agent

  1. What is the marker of bone turnover? What is the expected change after starting and stopping treatment?
  2. Do the effects of teriparatide persist after stopping therapy?
A
  1. osteocalcin.
  • After starting treatment, osteocalcin increases
  • After stopping treatment, it decreases
  1. NO.
64
Q

What imaging will be able to determine the age of a vertebral fracture for 1-2 years after a fracture?

A

nuclear medicine bone scan

(alk pho = 6-12 mos)

(MRI = 2-3 mos)

65
Q

Bisphosphonate holiday in patients with osteoporosis:
1. when to consider (length of treatment)
2. patient factors that warrant continued treatment
3. what sites should be used for monitoring?

A
  1. after 3 years of annual IV zoledronic acid or 5 years of oral bisphosphonate
  2. h/o hip or vertebral fractures, multiple fractures, T-score -2.5 or lower at the hip, or other factors placing them at “high risk” for fractures. (Can continue bisphosphonate for up to 10 yrs)
  3. mean total hip or unilateral total hip (NOT femoral neck)
66
Q

formula for calcium-to-creatinine clearance ratio

A

= [U(ca) S(cr)] / [S(ca) U(cr)]
less than 0.01 = FHH

67
Q

Indications for parathyroid surgery in asymptomatic patients with primary hyperparathyroidism (6)

A
  1. age < 50 yo
  2. serum calcium > 1.0 mg/dl above ULN
  3. T score -2.5 at any skeletal site on DEXA or vertebral compression fracture on imaging
  4. Creatinine clearance < 60
  5. kidney stones on imaging or nephrocalcinosis
  6. urinary calcium excretion > 400 mg/24 hr and increased stone risk by biochemical stone risk analysis
68
Q

How does denosumab affect calcium levels in renal impairment

A

can cause severe hypocalcemia, resulting in secondary hyperparathyroidism

69
Q

How does proton pump inhibitor use affect calcium?

A

can cause hypomagnesemic hypoparathyroidism –> hypocalcemia

Endocrinology (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions