Calcium Bone Disorders Flashcards
1
Q
only __ of bone is metabolically active
A
1% (only ionized calcium is metabolically active)
2
Q
t/f serum ionized ca > serum ca and albumin
A
true
3
Q
normal range of calcium levels
A
ionized ca 4.65-5.25 mg/dl
total serum ca: 8.5-10.5 mg/dl
4
Q
what is pseudohypocalcemia
A
total plasma ca is low but ionized ca is normal
5
Q
what is pseudohypercalcemia
A
elevation in the serum total ca concentration without any rise in serum ionized ca concentration
6
Q
corrected ca
A
measured total ca + (0.8 x (4.0-albumin))
serum total calcium concentration falls approximately 0.8 mg/dl for every 1 g/dl reduction in serum albumin concentration
7
Q
pth effects
A
works on bone to increase osteoclast activity
works on kidney to increase ca reabsorption in kidney
works indirectly on intestines to increase ca absorption from food (with help of vitd)
8
Q
hepatic conversion of vit d
A
enzyme: cyp27a1 or sterol 27-hydroxylase
product: 25-hydroxyvitamin D (inactive)
9
Q
renal conversion of vit d
A
enzyme: cyp27b1 or 25-dihydroxyvitamin d1-1-alpha hydroxylase
product: 1,25oh2d or calcitriol (active)
10
Q
vitamin d supplements
A
vitd2 (ergocalciferol): 10,000-50,000 iu vit d3 (cholecalciferol): 400-5,000 iu
11
Q
what produces calcitonin
A
nonfollicular cells of the thyroid (c cells)
12
Q
calcitonin effects
A
decreases tubular reabsorption of ca
impairs osteoclast mediated absorption
tumor marker for neuroendocrine diseases
13
Q
calcium homeostasis
A
calcium levels are high: ca inhibits pth, thyroid will release calcitonin
calcium levels are low: parathyroid glands will release pth (no inhibition)
14
Q
hormonal response to hypophosphatemia
A
low plasma po4 -> inc calcitriol -> absorption of ca and phosphate in the intestine
page 4
15
Q
conidtions that affect mineral homeostasis
A
primary hyperparathyroidism (inc pth) granulomatous disease (inc vitd) vit d deficiency (dec vitd) chronic renal disease (inc phosphate) hypoparathyroidism (dec pth)
16
Q
most common causes of hypercalcemia
A
primary hyperparathyroidism
malignancy
17
Q
mechanisms that elevate body ca
A
accelerated bone resorption
excessive gi absorption
dec renal excretion of ca
page 5
18
Q
complications of hypercalcemia
A
osteoporosis and fractures pancreatitis kidney stones hypertension cardiac arrythmias
19
Q
effects of ca on ecg
A
high ca = qt interval shorten
20
Q
diagnosis of hypercalcemia step 1
A
check repeat serum ca
correct ca for albumin
21
Q
diagnosis of hypercalcemia step 2
A
check for clinical signs: moans, groans, stones, and psychotic overtones
22
Q
diagnosis of hypercalcemia step 3
A
measure intact pth
elevated: phpt (primary hyperpth)
mild to upper normal: phpt or familal hypocalciuric hypercalcemia
low normal or low: non pth-mediated hypercalcemia
23
Q
definition of phpt
A
elevation of serum ionized calcium in the setting of an inappropriate elevation of pth
24
Q
management of hypercalcemia
A
volume expansion with isotonic saline loop diuretic calcitonin biphosphonates glucocorticoids denosumab calcimimetics hemodialysis
25
imaging studies for hypercalcemia
parathyroid sestamibi scan
26
criteria for parathyroid surgery
```
< 50 yo
serum ca 1.0 mg/dl above normal
(+) kidney stones or nephrocalcinosis
elevated 24h urine ca collection
reduced kidney fn
presence of vertebral fractures and osteoporosis
```
27
t/f inferior parathyroids are more likely to be ectopic
true, due to abnormal migration during embryogenesis
28
t/f patients with phpt are risk free after surgery
false, they're at risk for rapid influx of ca back into the bone due to the loss of stimulation by pth aka hungry bone syndrome = can lead to hypocalcemia
29
t/f most cases of hypocalcemia are autoimmune
false, 75% of cases are acquired
30
notable causes for low pth
parathyroid agenesis
di george syndrome
activating casr mutations
31
PE signs and symptoms for hypopth
```
trosseau's sign (hand)
chvostek's sign (facial nerve)
hyperreflexia
laryngeal spasm
seizures
```
32
complications of hypopth
```
hypercalcemia and hypercalciuria
impairment of well being and mood
cognitive dysfunction
basal ganglia calcifications
cataract
increased bone mass
```
33
what is pseudohypoparathyroidism
patients have an elevated PTH but the target organs are not responsive to the effects
34
vitamin d levels
deficient: < 50 nmol/ml or < 20 ng/ml
insufficient: 50-70 nmol/ml or 20-30 ng/mg
sufficient: 75-125 nmol/ml or 30-50 ng/ml
toxicity: >375 nmol/ml or >150 ng/ml
35
management in acute symptomatic hypocalcemia
iv calcium gluconate
36
other treatments for hypocalcemia
vit d repletion
high oral calcium intake (diet and supplement)
parenterally administered pth
magnesium
37
key regulator for phosphorus homeostasis
fgf23 + klotho, overproduced in ckd due to consistently elevated phosphate levels
38
physiological role and function of fgf23
short term: kidney
long term: intestines
result in return to normal serum phosphorus levels
39
normal phosphorus homeostasis
elevated phosphorus -> inc fgf23, dec 1,25oh2d3 -> dec ca in blood
dec ca in blood + dec calcitriol + inc phosphorus -> inc pth
40
chronic stimulation of parathyroid glands
ckd -> phosphate levels are constantly elevated -> inc fgf23 and pth
low ca levels and low 1,25oh2d3 -> inc pth -> parathyroid gland hyperplasia
41
t/f the abnormalities in secondary hyperparathyroidism covers all the abnormalities in ckd-mbd
true
42
what stage of ckd can ckd-mbd develop
stage 2, egfr = 60-89 ml/min
universal in stage 5
43
clinical manifestations of ckd-mbd
abnormalities in bone turnover, mineralization, volume linear growth, or strength
extra-skeletal calcification
44
fgf23 lowering therapy
phosphate restriction
phosphate biners
cinacalcet hydrochloride
parathyroidectomy
45
fgf23 increasing therapy
active vit d
| iv iron
46
treatment of secondary hyperparathyroidism: treatments of hyperphosphatemia
dietary phosphate restricion (dairy, red meats, sodas)
| use non-calcium containing phosphate binders to maintain normal serum phosphate
47
treatment of secondary hyperparathyroidism: treatment of vitd
cholecalciferol or ergocalciferol
NOT calcitriol, will further increase fgf
48
treatment of secondary hyperparathyroidism: treatment of hypocalcemia
mild and asymptomatic: not treated
treat vit d deficiency
49
treatment of secondary hyperparathyroidism: treatment of persistent hyperpth
calcimimetics
calcitriol
vit d analogs
parathyroidectomy
50
cause of tertiary hyperpth
excessive secretion of pth after long standing hyperpth leading to hypercalcemia
persistent hyperpth and development of hypercalcemia after renal transplant
51
treatment for tertiary hyperpth
parathyroid surgery
| calcimimetics-cinacalcet (SE: nausea)
52
moa of calcimimetics-cinacalcet
bind to and activate the calcium-sensing receptor in the parathyroid gland inhibiting pth
53
clinical manifestations of vitamin d deficiency
low vitd and ca
| high pth
54
groups at risk for vit d deficiency
```
breastfed infants
older patients
dark skin
patients with malabsorption syndromes
obese patients
```
55
treatment for people without vitd deficiency
600-800 iu per day
56
treatment for patients with normal absorptive capacity
100 units / 2.5 mcg until normal levels
57
treatment for patients with serum 25ohd <12 ng/ml
1250 mcg of vit d2 or d3 orally once/week for 6-8 wks
+ 20 mcg of vit d3 daily after
58
treatment for patients with serum vit d 12-20 ng/ml
20-25 mcg daily
59
diagnostic test for non-pth mediated hypercalcemia
measure pthrp and vit d metabolites
60
results for pthrp and vitd metabolites
elevated pthrp: humoral hypercal of malignancy
| elevated 1,25d: lymphoma, sarcoid, tb
61
possible diagnoses for normal pthrp and vitd
```
multiple myeloma
hyperthyroidism
vit a intoxication or other supplements
lithium
thiazides
```
62
t/f tb patients can take large quantities of vit d
false, if large quantities of 1,25oh2d3 are produced, a spillover effect can occur and result in hypercalcemia
63
treatment of choice for patients wit chronic granulomatous diseases and lymphoma
glucocorticoids
prednisone 20-40 mg/day
64
glucocorticoids moa
decreases intestinal absorption of dietary calcium due to excess vit d
decreases calcitriol production
65
most common cause of low-normal/low pth non-pth mediated hypercalcemia
humoral hypercalcemia of malignancy
66
treatmeent for humoral hypercalcemia of malignancy
bisphosphonates limit bone resorption
| denosumab is a monoclonal antibody to rankl
67
what is paget's disease
localized bone remodeling disorder characterized by increased bone resorption and accelerated bone formation
68
progression of paget's disease
overactive osteoclastic bone resorption -> compensatory increase in osteoblastic new bone formation -> structurally disorganized mosaic of woven and lamellar bone
69
initial osteolytic phase of paget
prominent bone resorption and hypervascularization
| "blade of grass" lesion
70
second phase of paget
haphazardly woven bone
| fibrous ct may replace normal bone marrow
71
final sclerotic phase of paget
bone resorption declines progressively leading to a hard, dense, less vascular pagetic bone
72
clinical manifestations of paget
usually asymptomatic with incidental findings of elevated alp or skeletal abnormality
symptoms: bone pain, secondary arthritis, fractures in the femur, compression of surrounding tissue
73
PE findings in paget
```
bowing of extremity
short stature with simian stance
extremity with an area of warmth and tenderness to palpation
bony deformities
leg length discrepancy
```
74
imaging findings in paget
```
bone resorption (black)
sclerosis (hyperdense)
cotton wool appearance = osteoporosis circumscripta
picture frame lesion
ivory vertebra
```
diffuse isotope uptake in bone scan
75
biochemical findings in paget
test of choice: ALP
elevated bone turnover markers
normal ca and phosphate
76
bone resorption markers
ctx
dpd, pyd, ntx, tacp
77
bone formation markers
oc, alp, balp, p1np
p1cp
78
treatment for paget
-dronates and calcitonin
79
t/f osteoporosis occurs more as people age but is not a natural part of aging
true
80
signs and symptoms of osteoporosis
back pain caused by fractured or collapsed vertebra
loss of height over time
stooped posture
bone fracture that occurs more easily than expected
81
complications of fractures
hip fractures: dvt and pe
vertebral fractures: restrictive lung disease
lumbar fractures: abdominal distention, early satiety, constipation
82
who should be screened for osteoporosis
women >65, men >70
postmenopausal women and men 50-69 with risk factors
fragility fracture at any age
height loss of 2 cm
all postmenopausal women with at least one who risk factor
83
screening tool for osteoporosis
frax screening tool
peripheral bone density test
osteoporosis screening tool for asians*
84
gold standard test for osteoporosis
dxa scan (central bone mineral density test)
lumbar spine, total proximal femur, femoral neck
85
bmd scores in young adults
normal: within 1 sd
osteopenia: 1-2.5 sd below
osteoporosis: =2.5 sd
severe osteoporosis: = 2.5 sd
86
tscore compared to bmd scores for 30 yo adult
normal: >/= -1 sd
osteopenia: -1 to -2.5
osteoporosis: at or below -2.5
severe osteoporosis: at or below -2.5 with >/= 1 fractures
87
indications for vertebral imaging
all women >/= 70 yo, men >/= 80 yo if the tscore is <1
women 65-69, men 75-79 if t score is <1.5
postmenopausal women 50-64, men 50-69 with risk factors
88
indication for pharmacologic treatment in osteoporosis
history of hip/vertebral fracture
osteoporosis based on bmd measurement
high risk postmenopausal women and men >/= 50 yo with tscores -1.0 and -2.5
adults with condition/taking medication that is associated with low bone mass or bone loss
89
osteoporosis medications that can stop bone loss
estrogens
| raloxifene
90
osteoporosis medications that can reduce vertebral fractures and further bone loss
calcitonin, pth, denosumab, strontium
91
moa of bisphosphonates
impairs ability of osteoclasts to form ruffled border and promote osteoclast apoptosis
92
moa of denosumab
antibody that binds to rankl -> osteoclast activity and survival is inhibited
can cause hypocalcemia
93
moa of teriparatide
anabolic agent that works like pth when administered intermittently
94
t/f estrogen/progestin therapy can be given to women with a history of heart disease and stroke
false
95
indications for estrogen agonist/antagonist (raloxifene)
risk for vertebral fractures
| risk for invasive breast cancer in postmenopausal women with osteoporosis
96
indications for calcitonin
hypercalcemia: IM/SC
| reduce re-occurrence of vertebral fractures: intranasal
97
indications for strontium ranelate
when other osteoporosis medicines are unsuitable
for vertebral and nonvertebral fractures
98
duration of osteoporosis treatment
3-5 years
discontinue bisphosphonates: stable bmd, no fractures, low risk for fractures
99
complications of bisphosphonates
atypical femoral fractures
| osteonecrosis of the jaw
