Metabolic Bone Diseases Flashcards
(103 cards)
1
Q
Metabolic Bone Diseases
A
Osteoporosis Paget's disease Osteomalacia Rickets Renal osteodystrophy
2
Q
Pathophysiology of Osteoporosis
A
Bone resorption outpaces bone deposition
3
Q
Negative Feedback Loop for Bone Remodeling
A
Hormonal process that maintains calcium homeostasis
4
Q
Types of Stress on the Skeleton
A
Mechanical
Gravitational
5
Q
What is osteoclast activity stimulated by?
A
PTH Calcitonin (low levels) GF IL-6 Lack of gonadal hormones
6
Q
Osteoblasts
A
Builders of bone matrix
Decreased number with aging
7
Q
How can the thyroid gland stimulate or inhibit osteoclast activity?
A
Hyperthyroidism: stimulate osteoclast activity
Increased plasma calcium: release of calcitonin
8
Q
Risk Factors for Osteoporosis
A
Age (>50) Gender Race (white, Asian) Activity level Diet Hormonal Meds: gonadal hormones Family history Medical history
9
Q
Components of Diet in Osteoporososis
A
ETOH
Tobacco
Low calcium intake or altered ability to absorb
10
Q
Hormonal Aspects with Osteoporosis
A
Amenorrhea Late menarche Early menopause Post menopausal state Low testosterone Low estrogen
11
Q
Medical Conditions Associated with Osteoporosis
A
Rheumatologic conditions Malabsorption syndromes Hypogonadism Hyperthyroidism Chronic kidney disease Chronic liver disease COPD Neurologic disorders (unable to ambulate or exercise) DM
12
Q
Medications that can Decrease Bone Density
A
Heparin Warfarin (+/-) Cyclosporine Medroxyprogesterone acetate (Provera) Vitamin A Loop diuretics Chemo drugs Antiseizure meds PPIs H2 blockers Antidepressants (TCA's & SSRI's) Glucocorticoids
13
Q
Prevention of Osteoporosis
A
Exercise Appropriate vitamin D and calcium intake Cessation of tobacco use ETOH in moderation Screening tests
14
Q
What is the standard test for the evaluation of bone mineral density?
A
DEXA scan
15
Q
Indications for a DEXA Scan
A
Currently treated or considering pharmacologic therapy for osteoporosis
Anyone not receiving therapy in whom evidence of bone loss would lead to treatment
Screening for osteoporosis
16
Q
DEXA Scan Screening Guidelines
A
Women >65
Men >70
Younger postmenopausal women and men with risk factors
Adults with fragility fractures
Condition associated with low bone mass
Medications associated with low bone mass
17
Q
Define T-Score
A
Bone mineral density compared to what is normally expected in a young healthy adult based on gender
18
Q
What T-score indicates osteoporosis?
A
Less than 2.5
19
Q
In what populations is a Z-score used instead of a T-score?
A
Premenopausal women Men younger than 50 Children African Americans Native Americans
20
Q
What is quantitative calcaneal ultrasonography effective at predicting?
A
Femoral neck, hip, & spine fractures
21
Q
Pros of Quantitative Calcaneal Ultrasonography
A
Lower cost than DEXA scan
Portable
No radiation exposure
Screening test NOT diagnosis
22
Q
Indications for Vertebral Imaging for Osteoporosis Screening
A
Bone testing not available in women >70 and men >80
T-scores of -1.5 in women 65-69 and men 75-79
Women 50-64 and men 50-69 with risk factors
Low trauma fracture
Historical height loss of 1.5”+
Prospective height loss of 0.8”+
Recent/ongoing long term glucocorticoid treatment
23
Q
After initial vertebral imaging, when should you reemerge to evaluate?
A
Loss of height
Suspect new vertebral fracture
New back pain
Postural change
24
Q
Work Up of Osteoporosis
A
H&P
Labs
+/- x-rays
DEXA scan
25
History in the Workup of Osteoporosis
Any history of disease
Family history
History of low vitamin D, prior bone density testing, or prior fractures
Medication review
26
Signs and Symptoms of Osteoporosis
Asymptomatic unless fracture
Gradual loss of height
Dowager's hump
27
Possible Labs to Diagnose Osteoporosis (Depends on comorbidities & history)
```
CBC
CMP
Serum magnesium
TSH
25-OH vitamin D
PTH
Testosterone (younger men)
24 H urine calcium
```
28
Indications for X-ray to Look for Osteopenia
Symptomatic patients
| Asymptomatic patients if vertebral fracture suspected
29
Non-Pharmacologic Treatment of Osteoporosis
Calcium
Vitamin D
Exercise
30
SE of Calcium
Nephrolithiasis
Dyspepsia
Constipation
Interfere with absorption of iron and thyroid hormone
31
Calcium Citrate vs. Calcium Carbonate
Citrate better with H2 blockers and PPIs
Citrate less likely to cause nephrolithiasis
Citrate harder to take
32
SE of Excessive Vitamin D Levels
Hypercalcemia
Hypercalciuria
Kidney stones
33
Guidelines for Pharmacologic Treatment of Osteoporosis
Age 50 and older + hip or vertebral fracture OR T-scores less than -2.5
T-score -1 to -2.5 in postmenopausal women and men 50 and older + 10 year hip fracture possibility >3% OR 10 year major fracture probability of >20%
34
Pharmacologic Options for Treatment of Osteoporosis
```
Bisphosphonates
Calcitonin
Estrogen agonist/antagonist
Hormone therapy
PTH 1-34
RANKL inhibitor
Tissue selective estrogen complex
```
35
Oral Bisphosphonates
Alendronate (Fosamax)
| Risedronate (Actonel)
36
IV Bisphosphonates
```
Zoledronic acid (Reclast)
Ibandronate (Boniva)
```
37
MOA of Bisphosphonates
Inhibit bone resorption by decreasing number and function of osteoclasts
38
What portion of oral bisphosphonates are taken up by the bone?
1-5% absorbed
| 30% of absorbed taken up by bones
39
Bisphosphonates Pre-treatment Screening and Testing
GFR >30-35 mL/min
Correct calcium and vitamin D deficiencies prior to administration
Review history for symptoms of abnormalities of esophagus or delayed gastric emptying
Ability to be upright for 30-60 minutes post oral dose
Recent fracture (wait)
Plans for dental extractions
40
Contraindications for Oral Bisphosphonates
Barrett's esophagus
Active upper Gi disease
D/C if symptoms of esophagitis occur
GFR less than 30-35 mL/min
41
Aldronate (Fosamax)
```
Generic
Low cost
Greater increase in BMD than Actonel
Well tolerated
Effective for 5-10 years
Daily or weekly
```
42
Risedronate (Actonel)
Less GI side effects
Well tolerated
Effective for up to 7 years
Daily, weekly, or monthly
43
Zoledronic Acid (Reclast)
Cannot tolerate oral therapy
Failure to respond to oral therapy
15 min IV infusion once a year
44
Ibandronate (Boniva)
No evidence of decreased hip fracture
| Q 3 months
45
SE of Bisphosphantates
```
Reflux
Esophagitis
Ulcers
Hypocalcemia
Musculoskeletal pain (large muscle groups)
Eye pain
Blurred vision
Conjunctivitis
Uveitis
Scleritis
Atypical fractures: subtrochanteric or lateral
Osteonecrosis of jaw
Flu-like symptoms post infusion
```
46
Risk Factors for Osteonecrosis of the Jaw
```
IV bisphosphonates
Anti-cancer therapy
Dental extractions
Dental implants
Poorly fitting dentures
Glucocorticoids
Smoking
Pre-existing dental disease
```
47
Duration of Oral Bisphosphonate Therapy
Reassess at 5 years
T-score >-2.5 discontinue
T-score less than -3.5 continue up to 10 years
48
Raloxifene (Evista): estrogen agonist/antagonist
Decrease risk of vertebral fracture by 30% with prior history of fracture
Decrease risk of vertebral fracture by 55% with no history of previous fracture
Less effective than estrogen and bisphosphonates
49
Indications for Raloxifene (Evista)
Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis
50
SE of Raloxifene (Evista)
DVT
Hot flashes
Endometrial cancer
51
Indications for Calcitonin
Osteoporosis in women >5 years post menopause
52
Calcitonin and Vertebral Fractures
Reduction by about 30% in persons with previous fractures
53
Contraindications of Calcitonin
History of allergy to salmon
54
SE of Calcitonin
Rhinitis
Epistaxis
Allergic reactions
55
Example of Hormone Replacement Therapy
Prempro (estrogen/progesterone)
56
Prempro and Osteoporosis
5 years duration
Decrease vertebral and hip fractures by 34%
Decrease other osteoporotic fractures by 23%
57
SE of Hormone Replacement Therapy
Increased risks of MI, CVA, invasive breast cancer, PE, DVT during treatment
No MI risk if within 10 years post menopause
58
MOA of Teriparatide (Forteo)
Stimulates bone formation
59
Indications for Teriparatide (Forteo)
Severe osteoporosis when other treatments have failed
60
Effects of Teriparatide (Forteo)
Decrease risk of vertebral fracture by 65%
| Decrease non-vertebral fracture by 53%
61
Administration and Duration of Teriparatide (Forteo)
A: subQ injection daily
D: 24 months max
62
SE of Teriparatide (Forteo)
Leg cramps
Nausea
Dizziness
Increased incidence of osteosarcoma (animal studies)
63
Contraindications of Teriparatide (Forteo)
```
At risk for osteosarcoma
Paget's disease
Prior RT of skeleton
Bone mets
Hypercalcemia
Hx of skeletal malignancy
```
64
MOA of Denosumab (Prolia)
Decreases bone absorption by inhibiting osteoclast activity
65
Indications for Denosumab (Prolia)
Postmenopausal women and men at high risk for fracture
| Cancer patients
66
Follow Up on Pharmacologic Therapy for Osteoporosis
Monitor for SE
Monitor for recurrent fractures
Yearly height management
Serial DEXA scans (every 2 years)
67
Treatment of Osteoporosis for Special Populations
Glucocorticoid induced
Renal failure (calcitriol)
Androgen deficiency (testosterone)
Malabsorption
68
What part of the body does Paget's Disease (Osteitis deformans) commonly involve?
```
Axial skeleton
Skull
Thoracolumbar spine
Pelvis
Long bones of the lower extremity
```
69
Pathophysiology of Paget's Disease
Increased rate of bone remodeling
Overgrowth of bone at a single or multiple sites
Impaired integrity of affected bone
70
Epidemiology of Paget's Disease
```
Genetic disorder
Etiology: possibly viral
Age: 55+
Men > women
Associated with osteosarcoma
```
71
Symptoms of Paget's Disease
```
Arthritis
Pain
Bone deformity
Fractures
Radiculopathy
Chronic back pain
Impaired functional status
Hearing loss
Headache
Vertigo
Tinnitus
Asyptomatic
```
72
Labs for Paget's Disease
Increased serum alkaline phosphatase
Normal calcium
Normal phosphorus
73
Imaging for Paget's Disease
X-ray
| Bone scan
74
Findings on X-rays for Paget's Disease
Mixed lytic and sclerotic lesions
Long bone bowing
Bone thickening and enlargement
75
Findings on Bone Scans for Paget's Disease
Increased bone remodeling and blood flow
76
Diagnosing Paget's Disease
```
H&P
X-rays
Elevated alkaline phosphatase
Baseline bone scan
Baseline calcium, 25-OH vitamin D, phosphorus
```
77
Goals of Treatment of Paget's Disease
Decrease pain
| Slow bone remodeling
78
Treatment of Paget's Disease
Supportive: calcium, vitamin D
| Bisphosphonates
79
Define Osteomalacia
Decreased mineralization of newly formed bone (soft bones)
80
Causes of Osteomalacia
Disorders that result in hypocalcemia, hypophosphatemia, or direct inhibition of the mineralization process
81
2 Main Causes of Osteomalacia
Insufficient calcium absorption from the intestine
| Phosphate deficiency
82
Etiology of Osteomalacia
```
Malabsorption
Gastric bypass surgery
Celiac sprue: malabsorption of vitamin D
Chronic hepatic disease: vitamin D stored in liver
Chronic kidney disease
```
83
Symptoms of Osteomalacia
```
Asymptomatic
Bone pain and muscle weakness
Bone tenderness
Fracture
Difficulty walking and waddling gait
Muscle spasms, cramps
Positive Chvostek's sign
Tingling/numbness
Inability to ambulate
```
84
Positive Chvostek's Sign
Twitching of the facial muscles in response to tapping over the area of the facial nerve
85
Work Up for Osteomalacia
```
Calcium
Phosphate
Alkaline phosphatase
25-OH vitamin D
PTH
Electrolytes
BUN and creatinine
Possible biopsy
```
86
Nutritional Deficiency and Osteomalacia Labs
```
Increased alkaline phosphatase
Decreased serum calcium and phosphorus
Decreased urinary calcium
Decreased 25-OH vitamin D
Increased PTH
```
87
X-ray Findings for Osteomalacia
Reduced bone density with thinning of the cortex
Looser pseudofractures
Fissures
Loss of radiologic distinctness of vertebral body trabecular and concavity of the vertebral bodies
88
Define Looser's Pseudofractures
Cortical infarctions
| Wide transverse lucencies traversing bone usually at right angles to involved cortex
89
Treatment of Osteomalacia
Correction of underlying cause
| Vitamin D supplementation
90
Most Common Fractures in Osteomalacia
Distal radius
| Proximal femur
91
What vitamin D supplement is used in renal and hepatic disease to treat osteomalacia?
Calcitriol
92
Define Rickets
Deficient mineralization at the growth plate
Prior to closure of the growth plates
Osteomalacia after closure of growth plates
93
Cause of Rickets
Decreased calcium
Decreased vitamin D
Renal phophate wasting
94
Define Renal Osteodystrophy
Bone disease secondary to chronic kidney failure
95
Types of Bone Disease Secondary to Renal Osteodystrophy
Osteitis fibrosa
Mixed uremic osteodystrophy
Osteomalacia
Adynamic bone
96
Effects of Renal Osteodystrophy
Calcium, phosphorus, vitmain D metabolism
PTH
Bone turnover
Bone mineralization, volume, linear growth
Bone strength
Extraskeletal calcification
97
Major Contributor to Renal Osteodystrophy
Secondary hyperparathyroidism
98
Secondary Hyperparathyroidism in Chronic Kidney Disease
```
GFR below 60 mL/min
Calcitriol deficiency
Hyperphosphatemia
Hypocalcemia
Increase in PTH
```
99
Pathophysiology of Osteitis Fibrosis
High turnover secondary to hyperparathyroidism
100
Pathophysiology of Dynamic Bone Disease
Low turnover due to suppression of the parathyroid glands
| Most common CKD related bone disease
101
Pathophysiology of Osteomalacia
Low turnover with abnormal mineralization
102
Pathophysiology of Mixed Uremic Osteodystrophy
Either high or low turnover and abnormal mineralization
103
Treatment of Parathyroidism in CKD
Dietary restriction of phosphorus
Supplemental active form of vitamin D
Phosphate binders
