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318 Cards in this Set
- Front
- Back
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how much of the body's calcium is stored in bone
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99%
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how much of the body's phosphorus is stored in bone
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85%
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what covers the inside and outside of flat bones
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periosteum
endosteum with spongy bone within, known as the diploe which forms trabeculae |
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what tissues are bones composed of
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osseous tissue
fibrous connective tissue cartilage vascular tissue lymphatic tissue adipose tissue nervous tissue |
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what is the epiphysis
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a thin layer of compact bone beneath the articular cartilage
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what is the periosteum
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a thick fibrous tissue that covers bone surfaces except for articular surfaces
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what are the two layers of the periosteum
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outer fibrous layer (dense connective tissue)
inner osteogenic layer (which remains active thoughout out life, contains osteoprogenitor cells and osteoblast) |
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what is teh nutrient foramen
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where nerve fibers, lymphatic vessels, and blood vessels enter the bone to supply the periostenum
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what connects the periostenum to the bone matrix
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strands of collagen
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what is the endosteum
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the delicate tissue membrane that covers the internal bone surface, including the trabeculae and canals
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what cell types are found in the endosteum
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osteoblast
osteoclast |
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most numerous cells in bone
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osteocytes which lasts several years
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bone tx with hypochlorite
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digests collagen
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bone tx with HCL
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removes mineral
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what are the components of bone matrix
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25% water
25% protein/organic matrix (95% collagen, 5% chondroiten sulfate) 50% hyrdroxxyapatite (calcium phosphate) and other minerals |
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osteocalcin
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is secreted into the blood by osteoclast and can be measured to determine bone activity
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hydroxyapatite
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Ca10PO4 6 OH2
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where are mineral crystals deposited?
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in the "hole" btwn lines of collagen fibers
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in children, th emedullary cavity of nearly every bone is filled with
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red bone marrow
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in young - mld aged adults, the shafts of long bones are filled with
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yellow marrow-- it no longer produces blood but can transform into red marrow in the event of severe or chronic anemia
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where is red marrow found in the adult skeleton
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axial
pectoral girdle pelvic girdle proximal heads of the humerus and femur |
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when does osteogenesis begin
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when mesenchymal cells provide the template for subsequent ossification
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before week 8, the human skeleton is made of
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fibrous membranes
hyaline cartilage |
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after week 8,
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bone tissue begins to replace fibrous membranes and hyaline cartilage
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what is intramembranous ossification
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the formation of bone directly from or within fibrous connective tissue membranes
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what is endochondrial ossification
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formation of bone from hyaline cartilage models
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which bones are formed by intramembranous ossification
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frontal, parietal, occipital, temporal
mandible clavicle |
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what is the first step in intramembranous ossification
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formation of the ossification center-- mesenchymal cells cluster together and secrete the organic components of bone matrix which b/cms mineralized through the crystallization of calcium salts
calcification causes mesenchymal cells to differentiate inot osteoblasts |
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what is the second step in intramembranous ossification
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the developing bone grows downward from the ossification center in small struts called spicules
blood vessels b/cm trapped within the growing bone |
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what is the third step of intramembranous ossification
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remodeling around trapped bld vessels produce osteons (compact bone)
connective tissue around the bone formes the fibrous layer of the periosteum while osteoblast close to teh bone surface b/cm endosteum |
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what is the first step of endochrondral ossification
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formation of a hyaline cartilage
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what happens after hyaline cartilage model forms
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condrocytes near the center of the shaft of the hyaline cartilage hypertropy. their lacunae expand and the matrix is reduced to struts that calcify. the chondrocytes are deprived of nutrients since diffusion cannot occur through calcififed cartilage and they die and disintegrate
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what happens after chondrocytes hypertophy
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-the perichondrium forms
-blood vessels grow into teh perichondrium -the cells of the inner layer of the perichondrium differentiate into ostoblasts -the osteoblast forms teh periosteum -the inner osteogenic layer produces a thin layer of bone aroumd the shaft of the cartilage -this forms the bony collar |
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-what happens after the formation of the bony collar
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-capillaries and fibroblasts migrate into the heart of the cartilage though the spaces left by the disentegrating chondrocytes
-the calcifed cartiaginous matrix breaks down -the fibroblasts differentiate into osteoblasts that make spongy bone -this forms the primary center of ossification |
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what happens after the formation of the primary ossification center
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osteoclasts break down the newly formed spongy bone and oepn up a medullar cavity in the center of the shaft
-osteoblasts move toward the epiphyses -the epiphyseal cartilage grows |
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what happens after the formation of the primary ossification center
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capillaries and ostoblasts migrate into the epiphyses
the epiphysis is transformed into spongy bone the epiphyseal plate -- a cartilaginous plate-- remanes at the juncture btwn the epiphysis and diaphysis |
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at puberty, bone length is incred by which hormones
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growth hormone
thyroid hormone sex hormone |
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when does the epiphyseal plate close
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when osteoblast produce bone faster than cartilage formation
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what are the zones of growth in the epiphyseal plate
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resting cartilage
proliferating cartilage hypertrophic cartilage calcifed cartilage |
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function of zone of resting cartilage
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anchors growth plate to bone
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function of zone of proliferating cartilage
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rapid chondrocyte division (staked coins)
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function of zone of hypertrophic cartilage
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chondrocytes enlarged and remain inc olumns
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function of zone of calcified cartilage
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thin zone, chondrocytes mostly dead since matrix calcified
chondroclasts remove matrix osteoblasts and capillaries move in to create bone over calcified cartilage |
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collagen is impregnanted with mineral to
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add stiffness to flexibility
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the stapes is a
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highly mineralized bone with no flexibility
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what is the disease state of hypomineralized bone
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osteomalacia-- excess osteoid material; bones can deform and not break
ricketts |
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what is the disease state of hypermineralized bone
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osteopetrosis (osteoclast can't remodel bone properly); bones are stiff but not tough and prone to fracture
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why did the skeleton evolve
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to be a resivour of calcium in a calcium deficent environment
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what are the phases of the remodeling cycle
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resorption
reversal formation resting |
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What happens during resorption
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osteoclasts remove organic and inorganic components of bone matrix;
osteoclasts forms a tight seal btwn it and bone via integrin receptors to create resorption space |
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what happens during the reversal phase
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mononuclear cells along the resorbed surface summon osteoblast into the cavity
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what happens in the formation phase
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osteoblast line on bone surface and produce collagen; collagen mineralizes after 21 days
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what forms osteocytes
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ostoblast
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what is the function of osteocytes?
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mechanosensors-- in tune with bones via caniliculi that connect it to the bone and other osteocytes
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what happens when bone formation is complete
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osteoblasts are no longer on the surface
lining cells-- (mononuclear cells) form a sheath across every bone surface; forms a blood bone layer that regulates the flow of ions into and out of the bone mineral continues to be deposited |
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what happens during the resting phase
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mononuclear lining cells remain
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what is the difference btwn remodeling in cancellous and cortical bone
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in cortical bone, osteoclast have to drill through the center of the bone and the osteoblast have to fill in a larger hole
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what forms haversian systems
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sheets of lamellar bone layed down by osteoblasts
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what are volkmans's canal
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blood vessels running perpendicular to long axis of bone
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where does remodeling occur at the highest rate
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areas rich in trabecular bone-- spine, femoral neck of femur, distal radius
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what is the timing of resorption
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2 wks for trabecular
4 wks for cortical |
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what is the timing for refomration
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7 wks trabecular
10 wks cortical |
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describe the remodeling in the bone
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highest negative balance on endosteal surface
positive balance on subperiosteal surface neutral in the cortex |
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what changes in bone occurs with age
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diameter increases but the cortical region thins
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why are male bones stronger than female bones during aging
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men are able to add more bone to perosteal surface than women
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what is the origin of osteoclasts
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circulating mononuclear cells
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what is the origin of osteoblasts
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fixed mesenchymal cells in marrow
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what accounts for slow bone loss in men and women
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osteoblast dysfunction (resporption cavity remains)
leads to thinning of trabecular plate |
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what accounts for rapid bone loss
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osteoclast hyperactivity; happens in postmenopausal women
leads to loss of trabecular plate |
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what is the architecutral changes in osteoporosis
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gradual thinning of trabecular plate
plate blcms rod like rod perforate horizontal rods drop out prefrentially |
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what happens to bone when estrogen levels fall
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proabsorptive cytokines (IL6, TNF a) incr in weeks leading to incr bone loss
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what is the effect of IL-6 on bone
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it stimulates osteoclastogenesis
-if blocked osteoclast activity can be inhibited |
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how does estrogen protect against bone loss
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inhibits IL6 activity at the bone
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what is RANK?
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a transcription factor impt for osteoclast formation that is expressed on the surface of osteoclast
-it is activated by RANKL binding |
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what is RANKL
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protein expressed by osteoblast and bone lining cells
it binds to RANK and activates RANK promoting osteoclast formation and survival |
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what is osteoprotegerin (OPG)
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a protein secreted by osteoblast that is a natural inhibitor of RANKL
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what is the effect of estrogen on RANKL pathway
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presence of estrogen leads to dcr synthesis of RANKL
loss of estrogen leads to incr in RANKL and more osteoclasts form |
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what is sclerostin
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negative regulator of bone formation
made by osteocytes |
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what is sclerostesosis
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a high bone mass disease c/b loss of function in sclerostin
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what are common disorders of bone and mineral metabolism
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osteoporosis
primary phyerparathyroidism vit d def rickets osteomalacia hypercalcemia of malignaey bone diesase of keiney failure hypomagnesemia |
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what are the functions of calcium
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skeletal integrity
excitation contraction coupling coagulation membrane stability and permeabilty cell secrertion of hormonae transmembrane signaling skeletal mineralization |
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what is the distribution of calcium in teh body
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1000g in body
990 g in skeleton: 99& is complexed, 1% is available for use 10 g extraskeleateal: 700mg tissues 300mg in blood |
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what are the forms of calicium in blood
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40% protein bound
50% ionized 10% complexed to anions |
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what are sx of hypocalcemia
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irritability and anxiety
paresthesis (esp around mouth) seizures laryngospasm bronchospasm hrt failure muscle cramps tetany (Chvostek's sign, Trousseu' sign) prolonged QT interval |
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what are sx of hypercalcemi
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dcr ability to concentrate
incr sleep requirement depression confusion and coma polyuria polydispia death arrhythmia bradycardia muscle weakness |
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tetany is a sign of
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impending hypocalcemic crisis (hand ulnar/laterally deviates)
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what is the normal range of total serum calcium levels in the blood
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8.5 - 10.4 mg/dl
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what states change serum calcium concentration
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albumin
anion concentration acid base status |
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how does changes in serum albumin affect changes in serum calcium
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total calcium changes in same direction
ionized calcium does not change |
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what is the equation for albumin corrected calcium
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for every gram teh serum albumin is below 4.0, add 0.8 mg to the total serum calcium
= 4 - serum albumin x 8 + total calcium |
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a rise in plasma phosphate
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dcr the ionized calcium
total serum calcium does not change (causes bone disesae in kidney pts) |
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acidosis leads to
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more H+ binding to albumin so that less Ca binds to albumin
ionized Ca incr total serum calcium doesn't chage |
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alkemia leads to
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less H+ on albumin = more binding sites for calcium
dcr in ionized calcium total serum calcium doesn't change |
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what is the only source of calcium
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diet
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what influeces calcium absorption
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amt of Ca in diet
ability of intestine to absorb it |
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where is calcium absorbed in the intestine
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duodenum
upper jejunum |
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how is calcium absorbed in the intestine
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-active transport, which requires vit D
-concentration dependent paracellular transport |
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what conditions dcr Ca absorption from the intestine
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intestinal diseases
aging estrogen deficiency |
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what is the major site of calcium balance
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kidney
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how much of the filtered calcium is actively reabsorbed or excreted to maintain calcium balance
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2%
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what regulates renal calcium excretion
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PTH
calcitriol |
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what is the normal urine calcium excretion
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100-300mg/day
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what 3 organs are invovled in calcium homeostasis
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bone
kidney intestin |
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what 3 hormones are involved in calcium homeostasis
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PTH
vit D calcitonin |
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in an adult with 1000 mg Ca intake a day what is the net absorptoin
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200mg
(350mg absorb, 150mg excreted) |
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what are the physiological functions of phosphorus
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skeletal integrity
acid base buffer |
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what is the normal serum levels of phosphate
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2.5-4.5mg/dl
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what are the forms of phosphate in the body
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45% ionized
40% complexed 15% protein bound |
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what infuences serum phosphate levels
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age
sex diet pH hormones phosphate levels are not tightly regulated |
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what is the only source of phosphate
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diet
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where is phosphate absorbed
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jejunum
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what are the mechanisms of phosphate absorption in the intestine
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passive transport
vit D dependent active transport absorption is directly related to intake |
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unlike calcium absorption from the intestine, phosphate absorption
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can occur in the absence of vit D
significant in renal failure where there are low levels of vit D--- serum phosphate can rise much higher than calcium |
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how much phosphate is filtered by the kidney a day
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700g
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how much of the filtered phosphate is reabsorbed
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80-90%
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what regulates kidney phosphorus excretion
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vitamin D
PTH phosphatonins |
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what are phosphatonins
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secreted by osteoblasts; way osteoblasts communicate with kidney
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what are the three main functions of bone cells
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modeling
remodeling Ca and PO4 balance |
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what receptors do osteoclast have
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calcitonin
cytokines RANKL TNFa |
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osteoblasts has receptors for what ligands
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PTH
1,24(OH)2D estrogen cytokines |
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what are the two functions of of osteoblasts
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synthesis bone collagen matrix
mineralize bone collagen matrix |
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what initiates the bone remodeling process
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the death of the osteocyte
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what ages does slow loss of bone take place
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30 - 40
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what perid does rapid loss take place
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40 -55 in menopausal women
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what are the calcitrophic hormones
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PTH
vit D |
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what are the functions of PTH
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regulate serum Ca and PO4
regulate bone remodeling regulate synthesis of vit D |
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when do the parathyroids secrete PTH
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when plasma calcium falls
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when is there a rapid drop in PTH levels
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when serum Ca is about 8-10mg/dL
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what is the mechanism underling PTH secretion
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parathyroid cells have a calcium sensing receptor on the membrane
CaSR is coupled by G protein to phospholipase C rise in extracellular ionized calcium cause incr intracellular ionized calcum and inhibition of PTH fall in extracellular ionized cl leads to dcr PTH secretion |
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what is the mechanism of PTH on the kidney
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PTH binds to PTHrP, coupled by Gs to adenylate cyclase
cAMP activates PKA PKA inhibits NaPO4 cotransporter at luminal surface |
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what is the effect of PTH on the proximal tubule of the kidney
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inhibits NaPO4 cotransport
incr 1,25 D synthesis |
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what is the effect of PTh on the distal tubule
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Incr Ca reabsorption
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what is the effect of PTH on the osteoblast
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incr formation which leads to incre release of both Ca and PO4
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what is indirect effect of PTH on the osteoclast
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incr resorption (long term) leading to incr release of Ca and PO3
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what is the indirect (mediated by vit D) effect of PTH on the upper jejunum
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incr Ca and PO4 absorption
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PTH leads to incr PO4 absorbtion from the intestion and resorption from the bone but net PO4 levels
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are unchanges since the kidneys NaPO4 trasporter is inhibited
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|
contrite
|
peniten, feeling or showing sorrow and regret for having done wrong; repentant- Her contrite tears did not influence the judge when he imposed sentence
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what are sources of vit D
|
D3 (cholecalciferol):
-UV light on 7-dehyrocholesterol in skin -fatty fish -cod liver oil D2 (ergocalciferol): -irradition of ergosterol in plants in yeast -fortified cereal, milk and bread |
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what is the RDA of Vit D
|
400-800IU
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what is the main circulating form of vit D, which is also measured to determine if someone has a deficency
|
25-OHD
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what is the control point in the kidney for regulating vit D
|
1a hydroxylase which will make active 1,24(OH2)D
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what stimulates 1a hydroxylase
|
low serum calcium
high PTH low phosphate |
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how does the kidney form inactive vit D
|
hydroxylating the 24 position instead of the 1 position
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how is vit d synthesized
|
D2 and D3 from diet is transported to liver
the liver hydroxylates the 25 carbon the kidney hydroxylates either the 1 carbon or 24 carbon |
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what are the target organs of vit D
|
intestine
bone kidney parathryoids |
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what are the molecular downstream effects of vit d
|
incr transcription of genes and synthesis of proteins taht control biological responses to vit D
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what is vit d effect on the parathyroid
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regulate its secretion via neg feedback
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what are the effects of vit D on the intestine
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incr Ca and PO4 absorption
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what are vit D effect on kidney
|
incr Ca and PO4 reabsorption
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what are vit d effect on bone
|
incr osteoclast bone resporption with PTH
incr osteoblast bone fomration |
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what is the overall effect of vit D
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incr plasma Ca and PO4 and incr bone mineralization
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where is calcitonin secreted
|
parafollicular C cells of thyroid
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what is major stimulus for calcitonin release
|
rise in plasma Ca
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what are actions of clacitonin
|
inhibits osteoclast bone resorption
incr urinary ca excretion |
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what is therapeutic use of calcitonin
|
mild forms osteoporosis
hypercalcemia |
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what are the physiological functions of magnesium
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structural (complexed with ca and po4 in bone)
-cellular energy transfer -essential component of ATP -genomic regulator -neuromuscular esxcitation contraction coupling |
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what is the body's distribution of magnesium
|
50-60% in skeleton
40% intracellular very little in ECF 55% serum Mg is ionized |
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what is the cavet in measuring serum Mg levels
|
they do not correlate well with body's store
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what is the regulation of Mg
|
30% of dietary Mg is absorbed
bone does not contribute to Mg balance kidney is main site of control and reflects body stores of Mg |
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what are the main causes of hypermagnesiemia
|
antacids
renal insufficency is a risk factor therapy of toxemia of pregnancy of premature labor to suppress neuromuscular activity |
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what are sx of hypermagnesemia
|
similar sx of hypercalcemia
depressed neuromuscular function |
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which magnesium disorder is most common, esp in hospitalized pts
|
hypomagnesium
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what are causes of hypomagnesemia
|
-Mg loss of intestine (esp lg bowel) (i.e. diarrhea)
-loop diruetics -cysplatin and other immunosuppresive agents -antitumor trugs -incr in urinary flow, sodium and/or calcium excretion |
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what occurs cocomittaly with hypocalcemia
|
hypomagnesemia
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how does hypomagnesemia affect calcium levels
|
PTH won't be secreted
PTH won't work well |
|
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what are sx of hypomagnesemia
|
-variable; masked by underlying illness
-asymptomatic -neuromuscular irritability (tetany) -cardiac arrhythmias -hypocalemia -hypokalemia |
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how do you tx hypomagnesemia
|
infuse a lot of magnesium (days)
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|
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what allows us to be in calcium balance
|
kidney which excretes teh amt that has been absorbed
|
|
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what is the turn over of calcium per day at the bone
|
500mg
|
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what are the causes of hypercalcemia
|
primary hyperparathyrodism
malignancy vitamin D excess incr bone turnover |
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what are the causes of hyperparathyroidism
|
Primary: adenoma
tertiary: after long standing secondary hyperparathyroidsm (As in renal failure) an autonomous nodule develops lithium |
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what are causes of malignancy related hypercalcemia
|
PTHrP
cytokines and incr vit D local osteolysis |
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what are cuases of incr bone turnover
|
hyperthyroidsim
immobilization + Paget's disease vit A |
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what are miscellaneous causes of hypercalceima
|
thiazides
Ca based antiacids adrenal insufficency |
|
|
what are causes of vitamin D excess related hypercalcemia
|
granulomas (sarcoid, TB, histo, WEgners)
vit D intoxication |
|
|
what is primary hyperparathyrodism
|
common endocrine disorder characterized by incompletely regulated, excessive secretion of PTH from teh parathyroid glands
|
|
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hyperparathyrodism is associated with
|
elevated serum Ca
high PTH levels |
|
|
normal PTH levels in pts with primary hyperparathyrodism
|
is considered abnormal since PTH levels should be supressed
|
|
|
what are CXR signs of osteitis fibrosa cystica
|
salt and pepper granulations of skull
bone resorption of phalanges |
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what is osteitis fibrosa cystica
|
bone changes caused by severe hyperparathyrodism
|
|
|
what is the modern clinical profile of primary hyperparathyroidism
|
-asymptomatic (80%)
-hypercalciuria (39%) -nephrolithias (17%) -overt skeletal disease (1%) |
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what are the biochemial findings in pts with primary hyperparathyroidsm
|
hypercalcemia
elevated PTH high active vit D |
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why is active vit D levels high in primary hyperparathyrodism
|
PTH stimulates 1a hydroxylase
|
|
|
densitometric bone findings in hyperparathyrodism (DXA) (dual energy X ray absorptiometry)
|
gold standard for osteoporosis
|
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what is the relationship btwn bone mineral density and fracture risk
|
for every 1 SD below normal bone density, risk of fracture incrs 2 fold
|
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what BMD changes do you see in the spine, femoral neck and radius in postmenopausal women with primary hyperparathyrodism
|
radius density has the greatest dcr
lumbar spine retains most of its density |
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which bone has high cortical bone composition
|
distal radius
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which bone has high cancellous bone composition
|
lumbar spine
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parathyroid hormone is most catabolic for which bone
|
cortical
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PTH is anabolic for which bone
|
cancellous (lumbar spine)
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what are guidelines that indicate parathyroid removal to tx hyperparathryodism
|
hypercalcemia >1mg/dL above normal
stone or overt bone disease reduced bone density younger than 50 |
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if hypercalcemia is not due to parathyroid secretion and PTH levels are low
|
it can be c/b by malignancy
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what is the eitology of humoral hypercalcemia of malignancy
|
malignant tumors synthesize and secrete a factor that stimulate osteoclast mediated bone resorption
|
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what is the criteria for PTHrP HHM
|
-produced by tumor
-blood levels correlates with hypercalcemia -mimics the clinical syndrome -reducing the PTHrP buder reverses hypercalcemia |
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which malignancies are associated with high levels of PTHrP
|
-HTLV T cell lymphoma
-classical squamous cell carcinoma -adenocarcinoma -breast carcinoma -myeloma and other hematological malignancies |
|
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what are potential physiological functions of PTHrP
|
lactation
placental calcium transport bone growth smooth muscle function |
|
|
what are clinical features of hypercalcemia
|
constitutional
CNS - disoriented, incr sleep GI - anorexia, constipated renal - polyuria cardiovascular- shortened QT interval |
|
|
what factors determine if a pt will have sx of hypercalcemia
|
how high serum Ca is
the rate of rise of serum Ca how long Ca has been elevated individual variability |
|
|
what is the pathophysiology of acute hypercalcemia
|
1. stimulus to hypercalcemia
2. hypercalcemia b/cms symptomatic 3. worsening hypercalcemia 4. reduced plasma volume |
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when should hypercalcemia be treated emergently
|
calcium greater than 14 (or in btwn 12-14)
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|
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what is the general approach to management to hypercalcemia
|
-IV saline (to correct possible volume depletion c/b hypercalcemia induced urinary salt wasting)
-diuresis (furosemide) -calcitonin -bisphosphonates -dialysis (if necessary) -mobilization |
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what is the specific management of hypercalcemia
|
bisphosphonates (zoledronate, pamidronate)
|
|
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mechanism of bisphosphonate action
|
high affinity for bone
get engulfed by osteoclast and disrupt its function |
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what factors are related to existing stimulus to hypercalcemia
|
-osteoclast activation
-renal tubular conservation of calcium (due to PTH) -reduced mobility |
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when hypercalcemia b/cms sx what sx are seen
|
polyuria
polydyspia anorexia |
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what are complications of anorexia in hypercalcemia
|
reduced fluid intake, continued polyuria and dehydration.
dehydration leads to reduced plasma volume, impaired renal function, reduced renal calcium clearence and worsening hypercalcemia |
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which IV bisphosponates are used for emergent lowering of hypercalcemia
|
zoledronate
pamidronate |
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what are adverse effects of pamidronate and zoledronate
|
acute phase reaction
mild transient fever transient leukopenia small reduction in serum phosphate hypocalcemia |
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how does calcitonin tx hypercalcemia
|
osteoclast inhibitor
calciuretic rapid reduction in calcium but weak and short lived effect |
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what are the causes of hypocalcemia
|
-hypoparathyroidsim
-pseudohypoparathyroidms (c/b contrast agents) -vit D defiency -chronic renal failure -accelerated net bone formation -calcium sequestration |
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what are causes of hypoparathyroidism
|
-autoimmune (polyglandular autoimmune syndrome type I, anti CaSR antibodies)
-iatrogenic (surgery, radiation) -hypomagnesium and acute and severe hypermagnesium -hemochromatosis |
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what are causes of pseudohypoparathyroidism
|
PTH endo organ resistance
|
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what are causes of vit D deficencey or resistance which can lead to hypocalcemia
|
sunlight deprivation
GI disese/fat malabsorption -anticonvulsants, rifampin, ketoconazole, F-FU, leucovorin |
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how does chronic renal failure lead to hypocalcemia
|
dcr vit D production
incr phosphate from dcr clearance |
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what are causes of calcium sequestration that can lead to hypocalcemia
|
pancreatitis
citrate excess (after blood transfusion) acute incr in phosfate (ARF, rhabdomyolysis, tumor lysis) |
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if you have hypoparathryodism, when your calcium drops
|
there is no response from parathyroid and PTH levels are low
|
|
|
mild hyupomagnesima
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leads to incr PTH
|
|
|
severe hypomagnesium
|
leads to dcr in PTH
|
|
|
pts with severe hypomagnesimia leads to
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dcr PTH secretion
dcr 1,25 activation dcr PTH action |
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what are the goals emergent tx hypomagnesium
|
alleviate sx and symptoms
correct hypocalcmei and hypokalemia |
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what is secondary hyperparathyroidism
|
high PTH to correct for hypocalcemia
|
|
|
what are clincial features of hypocalcemia
|
neuromuscular irritability
renal osteodystrophy |
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what are signs of neuromuscular irritability assoc with hypocalcemia
|
perioral paresthesias
cramps Chvostek's sign Trousseu's sx laryngo, or broncho, or carpal spasm depression psychosis icr ICP seizures prolonged QT interval |
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what is renal osteodystrophy
|
dcr vit D and incr PTH in renal failure which leads to osteomalacia an osteitits fibrosa cystica
|
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what is a Chvostek's sign
|
tapping facial nerve leads to contraction of facial muscles
|
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what is the Trousseu's sign
|
inflating BP cuff leads to carpal spasm
|
|
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what are are indications for acute tx of hypocalcemia
|
-sx
-no sx but serum calcium corrected for serum albumin less thatn 7.5mg/dL -hx of seizures -previous compression fracture |
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what is used to tx acute hypocalcemia
|
calcium gluconate
|
|
|
how is chronic hypocalcemia tx
|
oral calcium
oral vit D |
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|
what is calcitriol
|
active vit D
|
|
|
what is hypercalcemic crisis
|
when calcium levels rise abruptly to 13-15 leading to polyuria, dehydration, coma
|
|
|
phosphate retention and secondary hyperparathyroidism lead to
|
chronic renal failure
PTH reduces permeability of BM high phosphate damages the parenchyma |
|
|
describe the bone in osteoporosis
|
spaces in btwn bone b/cms wider and filled with marrow making it weak
|
|
|
what is the prevlance of ostoprosis
|
8 million women 2 million men
|
|
|
prevelance of osteopenia
|
34 million
|
|
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where are the most risky sites of fractures in osteopoorosis
|
spine
hip wrist |
|
|
hip and wrist fractures
|
are often painful
|
|
|
spine fractures
|
can be unfelt
|
|
|
what is the morbidity after hip facture
|
incr risk of death, permanent disability, unable to walk indp, or unable to carry out at least one ADL
|
|
|
what is teh morbidity after vertebral fracture
|
not as severe as hip
-back pain -loss of ht -deformity: kyphosis, protuberant abdomen -reduced pulmonary function -diminised quality of life -dependent on narcotic analgesic -sleep disorder |
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|
bone remodeling in postmenopausal women
|
always leads to a net bone loss
|
|
|
osteoprosis is a problem of
|
quantity and quality (horizontal beams are lost)
|
|
|
what is osteporosis
|
skeletal disorder charactherized by comprommied bone strength leading to incr risk of fracture
|
|
|
what are the determinants of bone strenght
|
bone density
rate of turnover microarchitecture bone size and shape damage accumulation mineralization matrix quality |
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|
at the same bone density a larger bone size
|
protects against fractures
|
|
|
what are lifestyle risk factors for osteoporosis
|
low calcium intake
vit D insufficency high caffeine (which leads to ca loss in urine) alcohol smoking falling immobilization thinness |
|
|
what are causes of secondary osteoporosis
|
hyperthyroidism
hyperthyroidism hypogonadism cushing syndrome diabetes mellitus type i vit d def malabsorption syndromes *glucocorticoid/steroids anticonvulsants rheumatoid arthritis myeloma |
|
|
what are medications associated with osteoporosis
|
glucocorticoids
cyclosporin cytotoxic drugs anticonvulsants excessive thyorid hormone heparin GnRH antagonists progestin only birth control aromatase inhibitors |
|
|
how do glucocorticoids cause bone loss
|
block Ca absorption in intestine
icr urinary excretion of Ca lower LH/FSH and estrogen incr osteoclast activity dcr number and function of osteoblasts |
|
|
pts who are about to start glucocorticoid therapy should
|
have a bone density scan
|
|
|
gold standard of dx osteoporosis
|
DXA bone mineral density testing
|
|
|
how is DXA used
|
-measures spine, hip and wrist
-lg normative data base -safe - |
|
|
BMD =
|
grams of calcium/cm2
|
|
|
t score from DXA
|
compared to young normal adults
predictive of pts risk of having a fracture |
|
|
z score from DXA
|
how pt differs from other pts of same age, race and gender;
SD from aged matched mean if more than 2 SD from aged matched mean, likely another underlying reason of osteoporosis |
|
|
what are the WHO osteoporosis guidelines in postmenopausal caucasian women
|
if t score is greater than -1 = normal
if t score is btwn -2.5 and -1 = osteopenia if t score is less than -2.5 = osteoporosis |
|
|
who should have a bone density test
|
women over 65
men over 70 -postmenopausal women with fragility fractures -women and men on or starting steroids -post menopausal women and men less than 70 with risk factors (thin, early menopause, smoking, fhx of hip fracture, secondary cause of osteoporosis) |
|
|
postmenopausal osteopenic women (-1-- -2.5)
|
have incr risk of fracture
|
|
|
most fractures occur in women with osteopenia b/c
|
there are more numerous than women with osteoporosis though fracture rate is higher in osteoporosis
|
|
|
for a given BMD, risk of fracture increases with
|
age
|
|
|
what is the FRAX WHO risk tool
|
gives the 10 year probability of having a fracture in osteopenic women
|
|
|
who should be tx for osteopenia/osteoporosis
|
-hx of hip or vertebral fracture
-BMD t score less than -2.5 at femoral neck or spine -BMD t score btwn -1.0 and -2.5 -if 3% or greater chance of hip fracture or 20% or greater of major osteoprotic fracture, for next 10 yrs |
|
|
what is osteomalacia
|
deficency of minerals in the bone leading to soft bone
|
|
|
what are sx of osteomalacia
|
diffuse dull bone pain
tenderness and muscle weakness waddling gait fractures with little trauma |
|
|
what are xray findings of osteomalacia
|
dcr bone density with blurring and deformity
|
|
|
most common cause of osteomalacia
|
vit d deficency
|
|
|
what is rickets
|
osteomalacia in children
-widening of ends of long bones -bowing |
|
|
normal vit levels
|
30ng/mL
|
|
|
bone disese in renal insufficency results from
|
dcr excretion of phosphate by damaged kidney leading ot hypocalcemia and high PTH
dcr vit d due to damaged kidney renal osteodystrophy |
|
|
what is paget's disease of the bone
|
focal areas of accelerated bone remodeling leading to overgrowth of bone
|
|
|
sx of paget's disease of bone
|
usually asympotmatic but can have pain and deformites
|
|
|
dx of paget's disease of bone
|
elevated alkaline phosphatase or x ray findings
|
|
|
tx of paget's disease of bone
|
bisphosphonate to ease pain and reduce rate of bone remodeling
monitor alkaline phosphatase |
|
|
what is osteogenesis imperfecta
|
inherited connective tissue disorder
brittle bone disease mutation in genes that code for proteins that combine to form type I collagen fractures with minimal trauma |
|
|
tx for osteogenesis imperfecta
|
bisphosphonates
|
|
|
what should the total calcium intake be
|
1200-1500mg
|
|
|
how much Ca should you take at a time and why
|
500-600mg with protein for better absorption
|
|
|
what is required with calcium carbonate
|
a source of acid (Gastric or food)
|
|
|
proton pumps inhibitors
|
can block calcium absorption
|
|
|
what are side effects of calcium carbonate
|
gas
bloating constipation |
|
|
why isn't 1,25 vit D levels used to measure index of vitamin D
|
-short half life
-not stored in fat |
|
|
what form of vit D is measured in blood
|
25-hydroxyvitimin D (the storage form)
|
|
|
when does parathryoid hormone level start to rise
|
when vit d drops to less than 30ng/ML
|
|
|
what is the daily recommendation of vit D
|
1200-1500 IU day
|
|
|
what are the 2 forms of vit D
|
D3 (cholecalciferol)
D2 ergocalciferol |
|
|
what are antiresorptives
|
dcr rate of bone remodeling
|
|
|
what are FDA approved antiresorptives for osteoporosis
|
estrogen
raloxifene bisphosphonates calcitonin denosumab |
|
|
what was the WHI finidng in estrogen and progestein or estrogen alone therapy
|
dcr risk of hip fractures
|
|
|
what are adverse risks of estrogen
|
VTE
stroke CAD breast cancer |
|
|
what are the official recommendations regarding estrogen use for osteoporosis
|
it should not be used as a primary threapy to prevent bone loss
it should not be used as a primary approach to tx osteoporosis |
|
|
what is an ideal SERM
|
skeletal and cardiovascular agonist
breast and uterus antagonist |
|
|
what drug class is raloxifene
|
SERM
|
|
|
how is calcitonin given
|
nasal spray
|
|
|
what are the adverse effects of raloxifene
|
incr hot flashes
incr leg cramps incr risk of DVT incr risk of PE stroke with incr mortality |
|
|
what are the benefits of raloxifene
|
incr bone mass
dcr vertebral fractures no breast tenderness no uterine bleeding dcr risk of breast cancer no incr cardiovascular risk |
|
|
what is the outcome of calcitonin therapy
|
reduced incidence in vertebral fractures
|
|
|
what is the outcome of calcitonin therapy
|
reduced incidence in vertebral fractures
|
|
|
what is a contraindication of calcitonin
|
pregnancy
|
|
|
what is a contraindication of calcitonin
|
pregnancy
|
|
|
what is the key biochemistry of bisphosphonates
|
a PCP bond that can't be metabolized by the body
an amino group |
|
|
what is the key biochemistry of bisphosphonates
|
a PCP bond that can't be metabolized by the body
an amino group |
|
|
what are the characteristics of oral bisphosphonates
|
-poorly absorbed
-must be taken in fasting state in morning with water and fast 30 min after - |
|
|
what are the characteristics of oral bisphosphonates
|
-poorly absorbed
-must be taken in fasting state in morning with water and fast 30 min after - |
|
|
what are side effects of bisphosphonates
|
GI intolerance
|
|
|
what are side effects of bisphosphonates
|
GI intolerance
|
|
|
what is the pathway bisphosphonates work
|
inhibit cholesterol pathway preventing the expression of anchoring proteins on osteoblasts
|
|
|
what is the pathway bisphosphonates work
|
inhibit cholesterol pathway preventing the expression of anchoring proteins on osteoblasts
|
|
|
which bisphosphonates reduce vertebral fractures
|
all
|
|
|
which bisphosphonates reduce vertebral fractures
|
all
|
|
|
which bisphosphonates reduce nonvertebral fractures
|
alendronate
|
|
|
which bisphosphonates reduce nonvertebral fractures
|
alendronate
|
|
|
what are adverse events assoc with bisphosphonates
|
-upper GI intolerance
-acute phase rxn (more with IV agents) -atypical fractures after long term use (oversuppression sydrome) -osteonecrosis of the jaw |
|
|
what are adverse events assoc with bisphosphonates
|
-upper GI intolerance
-acute phase rxn (more with IV agents) -atypical fractures after long term use (oversuppression sydrome) -osteonecrosis of the jaw |
|
|
what is denosumab
|
a human IgG antibody to RANKL; reduces all types of fractures
|
|
|
what is denosumab
|
a human IgG antibody to RANKL; reduces all types of fractures
|
|
|
what is an osteoanabolic
|
teriparatide or full lenghth PTH
|
|
|
how can PTH be anabolic
|
when given intermittently; leads to inhibition of sclerostin
|
|
|
what are the effects of teriperitide
|
dcr bone pain
improved trabecular connectivity |
