bones + osteoporosis

synathrosis joints

joints that have little or no movement

diarthrosis or synovial joionts

moveable joints, ex: between long bones

articular cartilage

covers bone in joint and provides smooth surface

joint capsule****

seals articular cavity

outer fibrous layer

inner synovial membrane

synovial fluid

lubricates articular cartilage

inorganic components of bone

calcium phosphate, hydroxyapatite

calcium balance

1000 mg intake

800 mg excreted in feces, 200 mg excreted in urine

PTH secretion causes

increased bone formation and resorption

increased renal reup of calcium and clearance of phosphate

osteoclasts

cause bone resorption (breakdown)

osteoblasts

cause bone formation

osteoclast maturation

PTH triggers RANKL (on osteoblast precursor)

RANKL binds to RANK (on osteoclast precursor)

then binds to M-CSF → triggers osteoclast maturation

osteoblast maturation

osteoclast bone resorption releases TGFβ, IGF1, cytokines

these factors trigger osteoblast maturation

osteoblast forms new bone to replace what was broken down

bone remodeling proteins

M-CSF (clast mat)

RANKL (blast pre)

RANK (clast pre)

OPG

binds to RANKL, prevent RANK from binding

deficiency → osteoporosis

PTH causes

increased calcium and phosphate absorption in GI tract via vitamin D

(high Ca suppresses, low Ca stimulates secretion)

vitamin d causes

increased calcium and phosphate absorption in GI tract

FGF23 causes

decreased phosphate reabsorption in the kidneys (increased clearance)

osteoporosis

silent skeletal disorder, increased risk for fracture

osteoporosis risk factors

older age, female, white/hispanic

low weight < 57 kg (bmi < 20)

smoker, excessive caffeine or alcohol

sedentary, early menopause, fam hx fracture

low Ca or vit D

diseases causing osteoporosis

hyperthyroidism, rheum arthritis, chronic liver disease

T1DM, crohn’s disease, celiac disease

drugs causing osteoporosis

phenytoin, heparin, steroids

too much thyroxine, -gliflozin, furosemide

antiretrovirals

osteoporosis signs and symptoms

fractures, loss of height

fragility fractures of hip, pelvis, spine, wrist, humerus from low trauma

fracture risk assessment (FRAX)

consider treatment in those with osteopenia and risk:

• >20% for hip, spine, humerus fracture

• >3% hip fracture

normal T score

-1 or higher

osteopenia T score

-1 to -2.5

osteoporosis T score

-2.5 or lower

severe osteoporosis T score

-2.5 or lower with hx frag fracture

osteoporosis diagnosis

T score -2.5 or lower

osteopenia + frag fracture of pelvis or humerus

osteopenia + FRAX > 20/3%

low trauma hip or spine fracture

high risk patients

osteoporosis (-2.5 or lower)

osteopenia + frag fracture of pelvis or humerus

osteopenia + FRAX > 20/3%

very high risk patients

hx fracture

T score below -3

FRAX > 30 or 4.5%

osteoporosis supplementation

calcium 1,200

vitamin D 1000-2000

calcium supplements

carbonate w food

citrate w/o

max single dose = 500 mg

ddi w thyoid, iron, ppi/h2 blocker

FDA approved agents for osteoporosis

bisphosphonates, ********

high risk osteoporosis treatment options

alendronate, risedronate, zoledronate, denosumab

high risk treatment reassessment

if stable for 5 years, consider drug holiday

if worsening assess for compliance then switch

very high risk osteoporosis treatment options

zoledronate, denosumab, teriparatide, abaloparatide, romosozumab

• if not working, can switch

• do not switch deno to teri or aba

bisphosphonates

alendronate, risedronate

zoledronate = iv/last line

ibrandronate does not reduce fractures

bisphosphonate considerations

must be taken 60 min before breakfast, with plain water, remain upright for 60 min

• can cause esophageal ulcer ^

ade = hypocalcemia, ONJ, atypical femur fracture

denosumab (prolia)

RANKL inhib

sc q6mon by hcp with calcium and vit d supp

ade = hypocalcemia, ONJ, atypical femur fracture

missed dose → vertebral fracture risk

teriparatide/abaloparatide

PTH analog

sc qd for 2 years

ade = orthostatic hypotension, ONJ, atypical femur fracture

missed dose → vertebral fracture risk

romosozumab

women only

sc q1mon by hcp for 1 year

BBW — MI, stroke