Hormones exam 4 bone health and osteoporosis

Bone remodelling functions (2)

repair micro-damage within the skeleton to maintain skeletal strength, supply calcium from the skeleton to maintain serum calcium

what are bone remodelling functions regulated by (3 main, first has 7 subtypes)

many circulating hormones (estrogens, androgens, vit D, PTH, IGF-1, TNF, ILs), nutrition, physical activity

resorbed bone to new bone formation ratio in healthy young adults and age 30-45

healthy young adults: resorbed bone = new bone formation
after age 30-45: resorbed bone > new bone formation

what does increased remodelling lead to

porous bone

how does bone remodelling work

osteoclasts eat away and then osteoblasts heal it immediately, work in parallel as a unit

Vitamin D amount per day

800-1000 units

Vit D deficiency in children vs adults

children- Rickets
adults- osteomalacia

increased risk for vid D deficiency (5)

elderly, northern latitudes, poor nutrition, malabsorption, chronic liver/renal disease

What compensates for Vid D deficiency induced fall in blood calcium

PTH hypersecretion- leads to renal phosphate wasting and leads to osteomalacia

Rickets description

in children, prior to epiphyseal fusion- vit D deficiency results in expansion of the growth plate, hypocalcemia and hypophosphatemia impairs mineralization of bone matrix proteins (osteomalacia), hypomineralized matrix is biomechanically inferior to normal bone- prone to bowing of weight bearing extremities and fractures

how many fractures does osteoporosis cause annually

8.9 million

statistics for how many people osteoporosis will affect

1 in 3 women over 50 and 1 in 5 men over 50

osteoporosis definition

reduction in the strength of bone leading to an increased risk of fractures

osteoporosis WHO definition

bone density with T score of -2.5 or lower (osteopenia is -1 s.d. below 0)

T scores explanation

standardize outcome compared to young population

z scores

standardize outcome compared to same age population

gold standard for bone mass measurement

dual energy x ray abroptiometry (DXA), highly accurate, two x-ray energies estimate area of mineralized tissue and divide by area to account for body size

other options for bone mass measurement

quantitative CT (pQCT)- used primarily to measure spine and hip, 3D- true density of mass of bone tissue per unit volume, expensive + more radiation exposure and less reproducable than DXA
ultrasound- measures bone mass by calculating the attenuation of the signal as it passes bone or the speed with which it passes the bone, low cost and used for screening

smiths fracture

flexion fracture of the radius

colles fracture

extension fracture of the radius, usually bc of a fall on an outstretched hand

Label top to bottom fracture risk of different bones as time goes on

hip, vertebrae, colles

Hip fractures per year USA

300,000

hip fracture issues

hospital admission + surgical intervention, can cause deep-vein thrombosis + pulmonary embolism (20-50%), mortality rate during year after surgery (5-20%), often beginning of the end and patients never recover

vertebral fractures per year USA

700,000

Vertebral fractures issues

relatively asymptomatic- diagnosed accidentally (radiography), pulmonary lung disease, height loss, kyphosis, pain/discomfort, slight increase in morbidity and mortality

healing of a fracture steps (4)

formation of blood clot bc innervation broken (very dangerous in older people), formation of cartilagious callus, formation of bony callus, bone remodeling

Risk factors for osteoporosis

ACCESS- alcohol use, corticosteroid use, calcium low, estrogen low, smoking, sedentary lifestyle

Effects of corticosteroids on bone metabolism (8 total)

decrease bone formation, decrease sex hormone secretion - increased bone resorption, decrease calcium absorption and decreased renal calcium reabsorption which both lead to decreased plasma Ca- increased PTH- increased remodelling
all leads to osteoporosis

glucocorticoid induced osteoporosis

therapeutic use- most common form of it, treatment often coincides with aging and menopause, no completely safe dose

glucocorticoid induced osteoporosis: mode of action (5)

inhibits osteoblast function and induces osteoblast apoptosis, increases bone resorption, decreases calcium absorption, increases urinary calcium loss, suppression of estrogens and androgens, induction of myopathy

treatment of glucocorticoid induced osteoporosis

only biphosophonates have been demonstrated to reduce fracture risk

estrogen and osteoporosis

decreases apoptosis of osteocytes- decreased activation of bone remodeling
decreases apoptosis of osteoblasts, decreases oxidative stress- maintenance of bone formation
increases apoptosis of osteoclasts and decreases RANKL-induced differentiation- decreased bone resorption

estrogen and menopause

menopause- cessation of ovarian function, no ovarian supply of estrogen

how does estrogen deficiency cause bone loss

activation of new bone remodeling sites, exaggeration of imbalance between bone resorption and bone formation, also loss of estrogen causes an increase in production of RANKL and an increase in osteoclast recruitment, estrogen also limits rate of apoptosis of osetoblasts so without it reduced life span of osteoblast and increased longevity of osteoclasts

Fracture data of estrogen-progestin therapy

50% reduction in osteoporotic fractures, but also increase in myocardial infarction and stroke

Nutritional recommendations

calcium: optimal calcium intake reduces bone loss and supress bone turnover
Vit D- taken together with calcium: 20-30% risk reduction
other nutrients: vitamin K, magnesium, calories, proteins

Physical activity and bones

prolonged inactivity can result in bone loss, physical activity most beneficial when started young before puberty, more active individuals are less likely to fall

exercise and neuromuscular function

improves coordination balance and strength which reduces risk of falling

treatment- nutritional and pharmacological

calcium and vit D supplements, biphosphonates, estrogen therapy, denosumab (antibody therapy vs RANK ligand)

biphosphonates

approved for treatment of osteoporosis, mode of action: induce apoptosis and osteoclasts function, leading to reduced osteoclast numbers and activity, 6-8% increased bone mass, 50% reduced 1 yr fracture

Denosumab

fully human monoclonal antibody to RANKL, binds to it and is inhibiting the formation of mature osteoclasts and reduces bone resorption, increases BMD in many places