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Ortho > Metabolic Bone Diseases > Flashcards

Metabolic Bone Diseases Flashcards

1
Q

What is the MC metabolic bone disease in the US?

A
  • osteoporosis
  • imbalance of bone homeostasis - bone resorption (osteoclastic activity) outpaces bone deposition (osteoblastic activity)
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2
Q

Describe bone remodeling?

A
  • cont process and regulated by 2 control loops
  • negative feedback loop: hormonal processes that maintains Ca homeostasis
  • stress on skeleton: mechanical and gravitational
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3
Q

What is the hormonaly control of bone homeostasis?

A
  • decreased plasma Ca++ leads to release of PTH from parathyroid and then this increases osteoclastic activity - releases Ca++ and PO4-
  • PTH has effects on kidney, bones and GI
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4
Q

Effects of PTH on body

A
  • kidney: increase Ca resorption in renal tubules, kidneys convert Vit D to its active form
  • bone: increased osteoclastic activity, release Ca++ and PO4-
  • GI tract: increase GI tract absorption of CA++ and PO4
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5
Q

Osteocalstic activity is responsible for? Stim by?

A
  • responsible for bone resorption
  • stimulated by PTH, calcitonin (inhibits osteoclastic activity), GF IL-6
  • lack of gonadal hormones:
    increased activity, vigor and lifespan of class, low estrogen increases IL-6
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6
Q

Osteoblastic activity? Effect of aging?

A
  • builders of bone matrix

- decreased number of osteoblasts w/ aging

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7
Q

Thyroid gland control over osteoclastic activity?

A
  • can stimulate or inhibit osteoclast activity
  • hyperthyroidism: thyroid hormones can stimulate osteoclast activity
  • increased plasma Ca = thyroid gland releases calcitonin
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8
Q

Effects of Calcitonin?

A
  • kidney: decreased Ca++ absorption, decreased PO4 absorption
  • bones: decreased osteoclast activity, decreased release of Ca++
  • GI: decreased Ca++ absorption
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9
Q

RFs for osteoporosis?

A
  • age: older than 50
  • gender (female)
  • race (white or Asian)
  • activity level (inactivity)
  • diet
  • hormonal
  • meds
  • family hx
  • medical hx
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10
Q

Diet’s effect on bone activity?

A
  • EToH
  • tobacco
  • low Ca intake or altered ability to absorb
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11
Q

Hormonal effect on bone activity?

A
  • amenorrhea
  • late menarche
  • early menopause
  • post menopausal state
  • low testosterone
  • low estrogen
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12
Q

Medical conditions that may be assoc w/ osteoporosis?

A
  • rheum conditions: Lupus, RA
  • malabsorption syndromes
  • hypogonadism
  • chronic kidney disease
  • chronic liver disease
  • COPD
  • hyperthyroidism
  • neuro disorders
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13
Q

Meds that have assoc w/ osteoporosis?

A
  • Heparin (Long term)
  • warfarin +/-
  • cyclosporine
  • medroxyprogesterone acetate (provera)
  • vit A
  • loop diuretics
  • chemo drugs
  • antiseizure meds
  • PPIs
  • H2 blockers
  • antidepressants (TCAs, SSRIs)
  • glucocorticoids
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14
Q

OSTEOPOROSIS mnemonic?

A
  • lOw Ca intake
  • Seizure meds
  • Thin build
  • Etoh
  • hypOgonadism
  • Previous fx
  • thyrOid excess
  • Race (white, Asian)
  • Other relatives w/ it
  • Steroids
  • Inactivity
  • Smoking
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15
Q

How can we prevent osteoporosis?

A
  • exercise (wt bearing and muscle strengthening)
  • approp vit D and Ca intake
  • cessation of tobacco use
  • avoidance of excessive EToH intake
  • screening test: measure ht yearly, DXA
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16
Q

What is a DEXA scan?

A
  • dual energy xray absorptiometry
  • std test for eval of bone mineral density
  • max wt for machine 300 lbs (some newer ones may support up to 400 lbs)
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17
Q

Indications for DEXA scan?

A
  • anyone currently being tx or considering pharm tx for osteoporosis
  • anyone not receiving therapy in whom evidence of bone loss would lead to tx
  • screening for osteoporosis
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18
Q

Screening guidelines for DEXA?

A
  • all women 65 and older, all men 70 and older regardless of RFs
  • younger postmenopausal womena nd men (50-70) w/ RFs
  • adults w/ fragility fxs
  • adults who have condition assoc w/ low bone mass (RA)
  • adults who take meds assoc w/ bone loss (steroids)
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19
Q

What is a T score?

A
  • bone mineral density compared to what is normally expected in young healthy adult (at their peak BMD) based on gender
  • less than -2.5 = osteoporisis
  • less than -2.5 + fragility fx = severe osteoporosis
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20
Q

What is a z score?

A
  • used in following pop:
    premenopausal women
    men younger than 50
    kids
  • -2.0 and lower: defined as below the expected range for age
  • above -2.0: w/in expected range for age
  • dx of osteoporosis in this group shouldn’t be based on BMD results alone
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21
Q

What is a quantitative calcaneal US?

A
  • effective at predicting femoral neck, hip and spine fx
  • lower cost than DXA
  • portable
  • no exposure to rad
  • used as screening test not for dx of osteoporosis
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22
Q

When is screening of vertebral imaging recommended?

A
  • if bone density testing isn’t available:
    all women 70 and older
    all men 80 and older
  • consider in pts w/ T score of -1.5:
    women 65-69
    men 75-79
    once initial test is done repeat if suspect new vertebral fx, loss of ht or new back pain or postural change
  • postmenopausal women 50-64 and men 50-69 w/ specific RFs
  • low trauma fx, hx ht loss of 1.5” or more, prospective ht loss of 08” or more, recent or ongoing long term steroid tx
  • this is generally used for sx pts
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23
Q

What is included in a osteoporosis work up?

A
  • hx: include questioning to determine if there is any hx of disease that may affect bone metabolism, family hx, anay hx of Vit D, prior bone density testing, prior fx, med review
  • physical
  • lab
  • +/- xrays
  • DXA scan
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24
Q

Signs and sxs of osteoporosis?

A
  • usually asx unless there is a fx
  • gradual loss of ht
  • dowager’s hump
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25
Q

Lab w/u for osteoporosis?

A
  • CBC
  • CMP
  • serum magnesium
  • TSH
  • 25-OH vit D
  • PTH
  • testosterone (in younger guys)
  • 24 hr urine Ca
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26
Q

When are Xrays indicated?

A
  • in sx pts
  • in asx pts if vertebral fx is suspected (or recent loss of ht)
  • can’t be used to dx osteoporosis but can suggest osteopenia
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27
Q

What is included in nonpharm tx for osteoporosis?

A
  • Ca
  • Vit D
  • exercise
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28
Q

Use of Ca as tx for osteoporosis? SEs?

A
  • 1200 mg daily (from diet and supplements)
  • SEs:
    nephrolithiasis
    dyspepsia
    constipation
    interfere w/ absorption of Fe and thyroid hormone
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29
Q

Is Ca citrate or Ca carbonate better tx?

A
  • when concomitant use of acid suppressing meds (H2 and PPIs) citrate is better absorbed
  • citrate may be less likely to cause kidney stones as well
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30
Q

Vit D - tx for osteoporosis? SEs?

A
  • 800 IU Vit D3 supp daily is recommended - may need more if initial vit D levels are low
  • SEs:
    excessive Vit D levels can cause hypercalcemia, hypercalciuria, kidney stones
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31
Q

NOF guidelines for pharm tx for osteoporosis?

A
  • age 50 and older
  • hip or verterbral fx
    or
  • T scores: -2.5 or less (measured at femoral neck, total hip or lumbar spine)
  • T score -1 to -2.5 in postmenopausal women and men older than 50
    plus
    10 yr hip probability greater than 3%
    or a 10 yr major osteoporosis fx probability of more than 20%
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32
Q

Pharm options for osteoporosis?

A
  • bisphosphonates***
  • Calcitonin
  • estrogen agonist/antagonist (raloxifene, evista)
  • hormone therapy
  • PTH 1-34 (teriparatide)
  • RANKL inhibitor (denosumab)
  • tissue selective estrogen complex (conjugated estrogens/bazedoxifene, Duaveetm)
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33
Q

Diff types of Bisphosphonates?

A
  • Alendronate (Fosamax)
  • Risedronate (Actonel)
  • Zoledronic acid (Reclast)
  • Ibandronate (boniva)
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34
Q

MOA of bisphosphonates?

Half life?

A
  • inhibit bone resorption by decreasing the number and fxn of osteoclasts
  • half life:
    in plasma: 1 hr
    in bone: may persist for lifetime
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35
Q

Pharmacokinetics of bisphosphonates?

A
  • only 1-5% of oral dose absorbed
  • 70% of absorbed dose is then cleared renally
  • the remaining 30% is taken up by the bone
36
Q

Bisphosphonates: pretx screening and testing?

A
  • GFR neeeds to be greater than 30-35 ml/min
  • correct Ca and Vit D deficiencies prior to admin:
    25 OH Vit D levels should be greater than 25-30 ng/ml
  • review hx and sxs for any abnormalities of esophagus (stricture or achalasia) or delayed gastric emptying
  • ability to remain upright for 30-60 min post oral dose (can erode the esophagus)
  • recent fx (wait 4-6 wks to start tx)
  • plans for dental extractions or implants: may increase risk of osteonecrosis of the jaw
37
Q

CIs to bisphosphonates?

A
  • Barrett’s esophagus
  • active upper GI disease
  • d/c if sxs of esophagitis occur
  • if GFR isn’t greater than 30-35 ml/min
38
Q

Admin of oral bisphosphonates?

A
  • specific recommendations in regards to eating or drinking prior to or after admin based on drug used
  • usually take on empty stomach, drink 8oz of water after
39
Q

Oral bisphophonates - DOC?

A
  • Aldronate (fosamax):
    generic, low cost, greater increase in BMD then actonel at all sites after 12 months of therapy, well tolerated and effected for 5-10 y, take daily or weekly, no diff in incidence of fx b/t the 2
  • Risedronate (actonel): may have less GI side effects, well tolerated and effective up to 7 y, daily, weekly or monthly
40
Q

IV therapy - Bisphosphonates?

A
  • Zoledronic acid 5mg/year (Reclast):
    if can’t tolerate oral therapy or if failure to respond to oral therapy, 15 min IV infusion once a year
  • Ibandronate (boniva): no evidence that it decreases hi[ fx, q 3 mo - no direct data regarding efficacy on IV formulation
41
Q

SEs of bisphosphonates?

A
  • GI: reflux, esophagitis, ulcers - esophageal cancer- if barrett’s goes unchecked
  • hypocalcemia (more common w/ IV)
  • MSK pain (been on long term)
  • ocular: eye pain, blurred vision, conjunctivitis, uveitis, scleritis
  • atypical fx: subtrochanteric, lateral
  • osteonecrosis of the jaw
  • flu like sxs post IV infusion: fever, myalgia, HA, arthralgia
42
Q

RFs for osteonecrosis of the jaw while on Bisphosphonates?

A
  • IV bisphosphonates
  • anticancer therapy
  • dental extractions
  • dental implants
  • poorly fitting dentures
  • glucocorticoids
  • smoking
  • pre-existing dental disease
43
Q

Duration of bisphophonate therapy?

A
  • Aldronate (fosamax) and Risedronate (actonel) at 5 yrs and then reassess need
  • low risk, no fx, T score greater than -2.5 may consider d/c
  • high risk, T score less than -3.5 continue therapy for up to 10 yrs
44
Q

When would estrogen agonist/antagonist (SERMs) be indicated? How effective is SERMs - Raloxifene (Evista)?

A
  • if pt failed bisphosphonates
  • Effectiveness:
    decrease risk of vertebral fxs by 30% in pts w/ a prior hx of vertebral fx
  • decrease risk of verterbal fx by 55% in pts w/o prior hx of vertebral fx
  • indicated for reduction in risk of invasive breast cancer in postmenopausal women w/ osteoporosis
  • less effective than estrogen and bisphosphonates
45
Q

Dosage and SEs of Ralxoifene (Evista)?

A
  • 60 mg once daily
  • side effects:
    DVT, hot flashes, endometrial cancer
46
Q

Use of Calcitonin in tx of osteoporosis?

A
  • Miacalcin or fortical:
  • FDA approved for tx of osteoporosis in women 5 years or more post menopause
  • reduction of vertebral fx by about 30% in persons w/ prior vertebral fx
  • hasn’t shown to reduce nonvertebral fxs
47
Q

MOA and SEs of Calcitonin?

A
  • antagonizes effects of PTH
  • 200 IU as single daily nasal spray or subq injection
  • CI w/ hx of allergy to salmon
  • SEs: rhinitis, epistaxis, allergic rxns
48
Q

When is HRT indicated?

A
  • only if failed other non-estrogen tx options
  • Prempo (estrogen/progesterone): 5 yrs of therapy, decreases vertebral and hip fxs by 34%, decreases other osteoporotic fx by 23%
49
Q

Downside of HRT?

A
  • increases risk of MI, CVA, invasive breast cancer, PE, DVT during 5 yrs of tx
  • no MI risk if starting tx w/in 10 yrs post menopause
50
Q

use of PTH (Forteo) in tx of osteoporosis?

A
  • unique in that it stimulates bone formation
  • for severe osteoporosis when other tx have failed: continue to fx 1 yr after bisphosphonate therapy, or intolerant to bisphosphonate therapy
51
Q

Length of tx of Forteo?

A
  • decrease risk of vertebral fx by 65%, decrease nonvertebral fx by 53%
  • 20 mcg subq injection daily
  • max duration: 24 months
  • monitor for alt in serum Ca
52
Q

SEs of Forteo? When should you avoid therapy?

A

SEs:

  • leg cramps, nausea, dizziness, increased incidence of osteosarcoma in animal studies
  • should avoid admin in pts at risk for osteosarcoma - paget’s disease, prior radiation therapy of the skeleton, bone mets, hypercalcemia, hx of skeletal malignancy
53
Q

What is Denosumab (Prolia)? Indications?

A
  • monoclonal AB
  • decreases bone absorption by inhibiting osteoclast activity
  • indicated for postmenopausal women and men at high risk of fx
  • used in cancer pts (breast and prostate)
54
Q

How do you follow a pt on Rx for osteoporosis?

A
  • monitor for SEs
  • monitor for recurrent fxs
  • yearly ht measurement
  • serial DXA scans: baseline and q 2 yrs
  • if lose 2 cm or more in ht (0.8 in) or more in a yr need repeat vertebral imaging to eval for new or additional vertebral fxs
  • DXA scan at initiation of tx and q 2 yrs
55
Q

Tx is needed for what special pop?

A
  • glucocorticoid induced
  • renal failure: calcitrol to enhance Ca absorption in renal dialysis pts
  • androgen deficiency
  • malabsorption
56
Q

What are other metabolic bone diseases?

A
  • paget disease
  • osteomalacia
  • rickets
  • renal osteodystrophy
57
Q

What is paget disease?

A
  • 2nd MC metabolic bone disease (osteitis deformans)
  • lesions may be solitary or occur at various sites
  • MC involves axial skeleton: skull, thoracolumbar spine, pelvis, long bones of lower extremity
58
Q

Mechanism of paget’s?

A
  • disease of osteoclast
  • increased rate of bone remodeling
  • overgrowth of bone at single or mult sites
  • impaired integrity of affected bone
  • genetic disorder
  • possible viral etiology
  • men more than women
  • assoc w/ osteosarcoma
59
Q

Sxs of Paget’s disease?

A
  • arthritis
  • pain
  • bone deformity
  • fxs
  • radiculopathy
  • chronic back pain
  • impaired fxnl status
  • hearing loss
  • HA
  • vertigo
  • tinnitus
  • asx (most)
60
Q

What are metabolic complications of Paget’s disease?

A
  • hypercalciuria

- increased incidence of kidney stones

61
Q

Lab findings in Paget’s disease?

A
  • increased serum Alkaline phosphatase
  • serum Ca should be normal unless fx or immobolization
  • serum phosphorus should be normal
62
Q

Imaging findings of Paget’s disease?

A

XR:
mixed lytic or sclerotic lesions, long bone bowing, bone thickening and enlargement

bone scan:
more sensitive than XR early on, increased bone remodeling and blood flow

63
Q

Dx of Paget’s?

A
  • H and P
  • XRs
  • elevated ALP
  • baseline bone scan needed
  • baseline serum Ca, 25-OH Vit D, phosphorus
64
Q

Tx of Paget’s?

A
  • goals: decrease pain, slow bone remodeling
  • supportive tx
  • Vit D 800 IU, Ca 1200 mg
  • Bisphosphonates:
    Alendronate (Fosamax - PO)
    Risedronate (Actonel - PO)
    Pamidronate (IV)
    Zoledronic acid (IV)
65
Q

What is osteomalacia?

A
  • decreased mineralization of newly formed bone
  • bone is soft but no loss of bone matrix
  • caused by disorders that result in hypocalcemia, hypophosphatemia, or direct inhibition of mineralization process
66
Q

What are the 2 main causes of osteomalacia?

A
  • insufficient Ca absorption from the intestine:
    lack of dietary Ca, VIt D deficiency or resistance (chronic liver disease and kidney failure)
  • phosphate deficiency: renal losses, decreased intestinal absorption
67
Q

Etiology of osteomalacia?

A
  • malabsorption
  • gastric bypass surgery
  • celiac sprue
  • chronic hepatic disease
  • chronic kidney disease
68
Q

Sxs of osteomalacia?

A
  • can be asx
  • bone pain and muscle weaknes (94%)
  • bone tenderness (88%)
  • fx (76%)
  • difficulty walking and waddling gait (24%)
  • muscle spasms, cramps, a + chvostek’s sign, tingling/numbness, or inability to ambulate (6-12%)
69
Q

W/u for osteomalacia?

A

Initial lab eval:

  • serum Ca++
  • phosphate
  • ALP
  • 25-hydroxyvitamin D (25-OHD)
  • PTH
  • lytes
  • BUN and Creatinine

Bone bx: may be needed if dx is in doubt or if cause is unknown

70
Q

Osteomalacia: lab results for nutritional deficiency?

A
  • increased ALP (95-100%)
  • decreased serum Ca and phosphorus (27-38%)
  • decrease in urinary Ca (87%)
  • decrease in 25-hydroxyvitamin D (calcidiol) - less than 15 ng/mL - 100%
  • PTH elevation: 100%
71
Q

Imaging for osteomalacia?

A
  • XR findings:
    MC finding: reduced bone density w/ thinning of cortex, looser pseudofxs, fissures, or narrow radiolucent lines, loss of radiologic distinctness of vertebral body trabeculae and concavity of vertebral bodies (codfish vertebrae)
72
Q

What are looser’s zones (fxs)?

A
  • cortical infarctions
  • wide transverse lucencies transversing bone usually at right angles to involved cortex
  • assoc most frequently w/ osteomalacia and rickets
  • pseuodfxs are considered a type of insufficiency fx
  • sclerotic irregular margins and are often symmetrical
73
Q

Tx of osteomalacia?

A
  • correct underlying cause
  • Vit D supp
    50,000 IU q weekx 6-8 wks
    check serum and urine Ca at 1 mo, 3, and then q 6-12 mo
  • check serum 25-OH-Vit D at 3-4 mo post initiation of therapy
74
Q

Osteomalacia characteristics? Tx?

A
  • fxs MC in distal radius and proximal femur
  • not a sig cause of hip fxs like osteoporosis
  • loss of mineralization may make xray image look poor quality
  • Calcitriol is a Vit D metabolite and used for Vit D replacement in renal and hepatic disease instead of Vit D2 or D3
75
Q

What is RIckets?

A
  • deficient mineralization at growth plate
  • rickets and osteomalacia usually occur together as long as growth plates are open
  • only osteomalacia occurs after the growth plates have fused
76
Q

Cause of Rickets?

A
  • decreased Ca
  • decreased Vit D
  • renal phosphate wasting
77
Q

What is renal osteodystrophy?

A
  • bone disease secondary to chronic kidney failure
78
Q

Types of bone disease secondary to renal failure?

A
  • osteitis fibrosa
  • mixed uremic osteodystrophy
  • osteomalacia
  • adynamic bone
79
Q

Mechanism of renal osteodystrophy?

A

Disorder of mineral and bone metabolism:

  • Ca, Phosphorus, Vit D metabolism
  • PTH
  • bone turnover
  • bone mineralization, volume, linear growth
  • bone strength
  • extraskeletal calcification also occurs
80
Q

What is a major contributor of renal osteodystrophy?

A

Secondary hyperparathyroidism

  • phosphate retention
  • decreased free ionized Ca
  • decreased 1,25 dihydroxyvit D
  • increase fibroblast growth factor
  • reduced expression of Vit D receptors, Ca sensing receptors, fibroblast growth factor receptor
81
Q

When does secondary hyperparathyroidism in CKD start?

A
  • starts when GFR below 60 ml/min
  • calcitriol deficiency and hyperphosphatemia = hypocalcemia
  • hypocalcemia causes an increase in PTH
82
Q

What can occur in renal osteodystrophy?

A
  • osteitis fibrosis: high turnover secondary to hyperparathyroidism
  • adynamic bone disease: low turnover, most common CKD related bone disease, due to suppression of parathyroid glands
  • osteomalacia: low turnover w/ abn. mineralization, not that common in CKD
  • mixed uremic osteodystrophy: either high or low turnover and abnormal mineralization
83
Q

Basis of tx for renal osteodystrophy?

A
  • tx is aimed at underlying problem
  • basis of tx for secondary hyperparathyroidism in CKD:
    dietary restrictions of phosphorus
    supplemental active form of Vit D (calcitriol), phosphate binders (if too much phosphate)
84
Q

a 55 yo F w/o complaints presents to office w/ concerns over a recent abnormal screening eval (heel san).
What T scores correlate w/ osteopenia?
What work up does she need?
what are some special areas in her hx to eval?
What is recommended tx at this time?

A
  • T score of -1 correlates w/ osteopenia
  • due to abnormal screening exam a DEXA is indicated, TSH, 25-OH Vit D, CMP, CBC
  • hx: meds, social, ROS for malabsorption, autoimmune dz
  • Recommended tx:
    exercise, Ca and Vit D supp
85
Q

a 56 yo man w/ hx of allergies, asthma, seizure disorder and recent thoracic compression fx that occurred while doing push ups

  • What w/u does he need?
  • What tx can you start even b/f getting dx studies back?
A
  • MOI of injury: low impact, fragility fx
  • W/u:
    document ht, labs: TSH, testosterone, Vit D, CMP, PTH
    dx studies: spine xray, DEXA scan
  • Tx: Ca and Vit supp
86
Q

70 yo man w/ 50 pack yr hx of smoking (quit 3 years ago), COPD, BMI of 22. He is active and golfs 3x a week and does yoga 2x a wk. He presents to clinic today for annual exam and for refills of HCTZ that he takes for HTN

  • What RFs does this pt have?
  • Does he need screening for osteoporosis?
A
  • RFs: COPD, tobacco use, low body wt

- He does meet screening for osteoporosis - DEXA scan

Ortho (24 decks)

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