Metabolic Bone dz Flashcards
Osteoporosis:
- MOA
- describe hormonal control of bone homeostasis
MOA:
-bone resorption (osteoclast activity) outpaces bone deposition (osteoblast activity)
Bone homeostasis:
-if there is a decrease in plasma calcium causes a release of PTH from the parathyroid which effects the kidney, bone, and GI to increase serum calcium.
Describe how PTH effects:
- kidney
- bone
- GI
Describe how Calcitonin effects:
- kidneys
- bone
- GI
Kidney: PTH causes increased Ca resorption in the renal tubules and kidneys convert vit D to its active form.
Bone: increased osteoclast activity, releases Ca and PO4.
GI: increased absorption of Ca and PO4
CALCITONIN:
Kidney: decreased calcium and PO4 absorption
Bones: decreases osteoclast activity and decreases release of calcium
GI: decreased calcium absorption.
Which hormones induce osteoclast activity?
Describe the effects of hyperthyroidism on calcium metabolism?
Describe how the thyroid inhibits osteoclast activity?
PTH, low calcitonin, GF, IL-6, low estrogen increases IL-6.
Hyperthyroidism:
-thyroid hormones stimulate osteoclast activity thereby increasing plasma calcium.
Thyroid gland inhibits osteoclast activity when plasma calcium is increased by releasing calcitonin.
Risk factors of Osteoporosis.
WHat is the mnemonic for remembering these risk factors?
- Age (greater than 50)
- Gender (female)
- White/Asian
- Diet (ETOH, Tobacco, low Ca intake)
- Inactivity
- Hormonal (low estrogen/ lowtestosterone)(amenorrhea, late menarche, early menopause, post menopausal state)
- Meds (heparin/warfarin, loop diuretics, chemo drugs, GLUCOCORTICOIDS)
- FHx
- Medical hx
OSTEOPOROSIS:
- lOw Ca intake
- Seizure meds
- Thin build
- Etoh
- hypOgonadism
- Previous fx
- thyrOid excess
- Race (white/asain)
- Other relatives with osteoporosis
- Steroids
- Inactivity
- Smoking
Prevention of osteoporosis?
Exercise (weight bearing and muscle strengthening)
Appropriate Vit D and Ca intake
Cessation of tobacco
Avoidance of excessive alcohol intake
Screening tests (measure height, DXA)
T/F, Dexa scan is the standard test for evaluation of bone mineral density?
What are the indications for Dexa scan?
What are the DEXA screening guidlines?
True.
Indications:
- anyone currently being treated or considering pharmacologic therapy for osteoporosis.
- screening for osteoporosis
Guidlines for Dexa:
-all women greater than 65YO and men older than 70YO regardless of risk factors
- postmenopausal women and men (50-70) w/ risk factors)
- adults w/ fragility fx
- adults who have a condition associated with low bone mass (rheumatoid arthritis)
- adults who take medications associated with bone loss (steroids)
What is a T-Score?
what is indicated if T score is less than -2.5? Less than -2.5 w/ fragility fx?
-1 to -2.5?
T-score is used in Dexa Scan.
T score less than -2.5 = osteoporosis
T-score less than -2.5 + fragility fx = severe osteoporosis.
-1 to -2.5 = osteopenia
(if -1 this means they are one standard deviation away from the rest of the population for that age)
Dexa Scan:
-when is a Z score used?
Z-score used in premenopausal women, men younger than 50YO, and children.
- African americans and native americans.
- *T-score used in caucasians
Which test is effective at PREDICTING femoral neck, hip, and spine fxs?
Quantitative calcaneal US.
*if they have abnormal results they need to be referred for DEXA Scan.
Osteoporosis WOrk up?
Osteoporosis non-pharm Tx?
Hx
PE
Lab: CBC. CMP, serum magnesium, TSH, 25-OH Vit D, PTH, Testosterone, 24Hr urine calcium
+/- Xray (in sx patients, in asymptomatic pts if vertebral fx suspec)
Dexa scan
Tx: Caclium 1200mg, Vit D 800IU, exercise.
Osteoporosis Tx:
- SE of calcium
- SE Vit D
SE Calcium: nephrolithiasis, constipation, dyspepsia
SE Vit d:
-hypercalcemia, hypercalciuria, kidney stones.
Indications for Pharmacologic tx of osteoporosis?
Indications:
-older than 50YO AND they have a hip or vertebral fx
OR
-T score less than or equal to -2.5.
-T score -1.0 to -2.5 in postmenopausal men/women age 50YO and older PLUS 10year hip fx probability of greater than 3% or a 10Y major osteoporosis fx probability of greater than 20%.
Pharmacologic Tx options for Osteoporosis
- Bisphosphonates**(DOC)
- Calcitonin
- Estrogen agonist/antagonist
- Hormone therapy
- Parathyroid hormone
- RANKL inhibitor (Denosumab)
- Tissue selective estrogen complex
Bisphosphonates:
- drugs
- route of admin
- MOA
- half life
- renal dosing?
- complications
- CI
Drugs & Route:
-Alendronate (Fosamax) & Risedronate (Actonel) are PO.
Zoledronic acid (Reclast) & Ibandronate (Boniva) are IV.
MOA: inhibit bone resorption by decreasing the number and function of osteoclasts.
Half life: 1hr in plasma, in bone may persist for a lifetime.
Renal dosing: GFR needs to be greater than 30-35ml/min
Complications:
-erosive esophagitis, (make sure they can remain upright and drink a big glass of water after they take a pill)
CI:
- barretts esophagus
- active upper GI Dz
- GFR less than 30-35ml/min
Bisphosphonates:
- admin directions
- duration of therapy?
Admin directions:
- take on an empty stomach, drink 8oz of water and remain sitting upright for 1hr.
- tx is daily, weekly or monthly for PO drugs.
Duration:
- at 5 years reassess the need, actually every time you see the pt you should reconsider if they need this therapy.
- after 10 years the medications have done what they are going to do. if your going to have them on it for over 10 years have a reason.
Bisphosphonate:
-SE
GI:
-reflux, esophagitis, ulcers
Hypocalcemia
MSK pain (along the spine or pain in the larger muscles groups such as the thighs or back)
Ocular (eye pain, blurred vision, conjunctivitis, uveitis, scleritis)
Atypical fx (sub trochanteric, lateral)
Osteonecrosis of the jaw** (MC with IV)
Flu-like sx post IV infusion (fever, myalgia, HA, arthralgia)
Estrogen agonists/antagonist:
- drug name
- indications
- SE
- use in men and women?
drug: Raloxifene (Evista)
Indications:
-reduction in risk of invasive breast CA in postmenopausal women with osteoporosis.
SE:
-DVT, hot flashes, endometiral CA.
NO!!!! ONLY USED IN WOMEN.
Calcitonin:
- drug names
- MOA
- CI
- SE
Drugs: Miacalcin or Fortical
MOA: antagonizes the effects of PTH
CI in those w/ salmon allergy
SE:
-rhinitis, epistaxis, allergic rxn
Hormone Replacement Therapy:
- drug name
- Risks
Drug: Prempro (estrogen/progesterone)
Risk:
-increased risk of MC, CVA, invasive breast cancer, PE, DVT….no MI risk if starting within 10years post menopaus. Should not continue this tx for more than 5 years.
Parathyroid Hormone:
- drug name
- indications
- duration
- SE
Drug: Teriparatide (Forteo)
Indications:
- severe osteoporosis when other tx failed.
- -continue to fx 1 year after bisphosphonate therapy
- -intolerant to bisphosphonate therapy
Duration: max duration is 24mo
SE:
- leg cramps, nausea, dizziness
- increased incidence of osteosarcoma
How do you follow pts on Rx therapy for osteoporosis?
Monitor SE
Montior recurrent fx
Yearly height measurement
Serial Dexa Scans (baseline and then every 2 years)
Paget Dz of the Bone
- MC affects which bones?
- pathophys
- sx
- complications
Bones: axial skeleton, skull, thoracolumbar spine, pelvis, long bones of the lower extremity (in order of frequency)
Patho:
-increased rate of bone remodeling, over growth of bone at a single or multiple site. Impaired integrity of affected bone.
Sx:
- most are asymptomatic**
- arthritis
- pain
- bone deformity
- fx
- radiculopathy
- chronic back pain
- impaired functional status
- hearing loss
- HA
- vertigo
- tinnitus
ComplicationS:
- hypercalciuria
- increased incidence of kidney stones.
Pagets Dz of Bone:
- labs
- imaging
- dx
- tx
Labs:
- increased serum alkaline phosphatase
- serum Ca should be normal unless fx or immobilization
- serum phosphorus should be normal
Imaging:
-xray: mixed lytic and sclerotic lesions, long bone bowing, bone thickening and enlargement
-Bone scan (increased bone remodeling and blood flow)
Dx:
- XRAYS
- elevated serum alkaline phosphatase.
Tx:
- supportive; decrease pain and slow bone remodeling
- Vit D 800iU and calcium 1200Mg
- Bisphosphonates:
- -Fozamax
- -Actonel
- -Reclast (Zoledronic Acid )
Osteomalacia:
- what is this?
- causes
What: decreased mineralization of newly formed bone. bone is soft but no loss of bone matrix.
Causes: disorders that result in hypocalcemia, hypophosphatemia or direct inhibition of the mineralization process.
- *Insufficient Ca absorption from the intestine (lack of dietary calcium, vit D deficiency or resistance d/t chronic liver** or kidney dz**)
- *Phosphate deficiency (renal losses, decreased intestinal absoprtion)
Osteomalacia:
- sx
- work up
Sx;
- asymptomatic
- bone pain and muscle weakness
- bone tenderness
- fx
- difficulty walking and waddling gait
- muscle spasm, crmaps, + CHvostek sign, tingling/numbness or inability to ambulate.
Chvostek sign = twitching of the facial muscles in response to tapping over the area of the facial nerve.
Work up:
- serum ca
- phosphate
- ALP
- 25-OHD
- PTH
- Electrolytes
- BUN and Creatinine
- bone bx
Osteomalacia:
- xray findings
- tx
Xray:
- reduces bone density w/ thinning of cortex
- fissures or narrowing radiolucent lines
- looser pseudofractures (cortical infarctions, wide transverse lucencies traversing bone usually at right angles to the involved cortex
Tx:
- correct underlying cause
- vit D supplementation
Osteomalacia:
- Fx MC found where?
- xray findings
Fx MC found in the distal radius and proximal femur.
Xray findings: loss of mineralization may make the xray look poor quality
Rickets:
- what is this?
- usually occurs with what other disorder?
- cause
What: deficient mineralization at the GROWTH PLATE.
Osteomalacia and rickets usually occur together as long as the growth plates are OPEN.
**Only osteomalacia occurs after the growth plates have fused.
Cause:
- decreased calcium
- decreased vit D
- renal phosphate wasting
Renal osteodystrophy:
- what is this?
- types of bone dz 2ndry to renal failure.
- tx
What: bone disease secondary to chronic kidney failure. Disorder of mineral and bone metabolism.
Cause:
- osteitis fibrosa
- mixed uremic osteodystrophy
- osteomalacia
- adynamic bone
- hyperparathyroidism secondary to CKD
KIDNEY DZ CAUSES BONE DZ
Tx:
-tx is aimed at the underlying problem.