metabolic bone disease

Question 1

cortical bone, trabecular bone, bru definition

Answer 1

cortical bone-outer layer of bone, function is primarily structural

Trabecular bone: bone within the marrow space, function is primarily metabolic

BRU: bone remodeling unit, including osteoclasts and osteoblasts at a single anatomical site

Question 2

Osteoporosis

Answer 2

a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture, bone strength reflects the integration of factors

Bone density, bone turnover, bone architecture, bone mineral

Question 3

Osteomalacia, secondary hyperparathyroidism, hypophosphatemic rickets, pagets disease

Answer 3

Osteomalacia: disorder characterized by impaired mineralization of quantitatively normal bone extracellular matrix

Secondary hyperparathyroidism- elevation of PTH resulting from low serum CA

Hypophosphatemic rickets: disorder characterized by lifelong osteomalacia due to low serum phophate

Pagets disease: acquired disorder characterized by unregulated, excessive focal bone remodeling

Question 4

bone components

Answer 4

Cortical and trabecular bone are constitiuted of the same cells and same matrix elements, but there are structural and functional differences

Cortical Bone- 80-90% of the volume is calcified, fulfills mainly a mechanical and protective function, always found on outside of bones and surrounds trabecular bone

Trabecular bone: 15-25% of volume is calcified, fulfills mainly a metabolic function, 20% of bone

Question 5

bone remodeling

Answer 5

cortical remodelling (haversion)

Cancellous remodelling

Remodeling cycle- resorption by osteoclasts is rapid, requires about 2 weeks, deposition and mineralization of new bone matrix is slow, requiring 4-6 months

Although most of the skeletal volume is cortical bone, about 80% of the remodeling takes place in trabecular bone

As bone surround osteoblasts, some undergo apoptosis while other become osteocyte

Question 6

bone is mechanically responsive

Answer 6

additional bone forms in response to habitual mechanical loading
Bone is lost in response to habitual mechanical unloading
Thus there is mechanical feedback regulation of skeletal mass

Osteocytes- osteoblasts descendants, connected to one another and surface cells by cytoplasmic processes encased by bony cnaliculi

Elicit remodelingresponse to mechanical stimuli (mechanosensors), produce factors that regulate bone and mineral
Sclerostin- inhibits bone formation
Phosphate regulators (FGF23, PHEX, MEPE, DMP1)

Question 7

osteoporosis is very common

Answer 7

WHO definition, a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture

Bone strength reflects the integration of 2 main features, bone density and bone quality

Question 8

BMD is only a mediocre predicror of fracture risk

Answer 8

While persons with low BMD have a higher fracture rate, more fractures occur in people without BMD defined osteoporosis than those with it

This is because the number of people without BMD-defined osteoporosis is much larger

Question 9

Verterbral deformity

Answer 9

More severe vertebral fractures predict fractures

Males have later puberty so greater stature, males bone are larger, Females have 2x riks of fracture

Higher steroid use–> increased bone fracture

Question 10

Bisphosphonates

Answer 10

inhibit conversion of mevalonate to farnesyl, inhibit protein farnesylation, cause osteoclast apoptosis

Oral bisphosphonates- alendronate, risedronate, ibandronate–> esophageal irritation,

IV bisphosphonates- pamidronate, zoledronic acid, ibandronate, acute phase reaction
Rare adverse effects of both are atypical fratures and osteonecrosis of the jaw

Oral bisphosphonates must be taken correctly- empty stomach, full glass water, no co-adminstered medications, food, or beverages, remain upright 30 minutes

Persistence at 1 year estimated at 50%, if otherwise appropriate, consider IV

Question 11

Denosumab

Answer 11

Rank is on osteoblasts when RANKL binds to the osteoblast–> osteoclasts

Denosumab binds to RANKL, so osteoclast activity, formation, and survival is inhibited

Injection every 6 months,
SE-hypocalcemia, ONJ, atypical fractures, rebound increase in bone resorption when stopped

Question 12

Estrogens and SERMs

Answer 12

Estrogens and SERMs (selective estrogen receptor modulators) decrease RANKL Production, and so reduce remodeling initiation rate

Hormones arent great, may be beneficial in early postmenopausal women

SE: thromboembolism, endometroal hyperplasia, endometrial cancer, breast cancer, SERMs (raloxifene, tamoxifen) are breast cancer protective, tamoxifen not labeled for osteoporosis

Some adverse estrogen effects may be attributable to oral route and hepatic first pass metabolism, transdermal may be a better choice, endometrial effects managed by progestins

Question 13

cslcitonin

Answer 13

not used really

Question 14

teriparatide and abaloparatide

Answer 14

Efficacy relies on short half life, action on osteoblasts is sustained, action on osteoclasts is transient

Net: increased matrix synthesis
Daily injection

like PTH

osteosarcomas in rodents

Question 15

Romososumab

Answer 15

antibody to sclerostin, dampens bone degredation and increases building

Question 16

Nutritional substrates

Answer 16

All fracture preventing drugs rely on adequate utrition, protein, calcium, vitamin D, and phosphate

Question 17

Hypophasphatemic disorders

Answer 17

Tumor- induced osteomalacia, autosomal dominant hypophasphatemic rickets, autosomal recessive hypophasphatemic rickets
Xlinked hypophasphatemic rickets

all include elevated or inapproprate levels of FGF23, hypophosphatemia, and osteomalacia

Question 18

Osteomalacia

Answer 18

adequate, normal organic bone extracellular matrix, but the matrix is undermineralized

Question 19

pagets bone disease

Answer 19

second most common bone disease after osteoporosis
Northern europeans, no symptoms usually
One or more bones, earliest lesion osteolytic (increase in osteoclasts, giant multinucleated osteoclast, nuclear/cytoplasmic inclusions), subsequent increase in osteoblasts and chaotic bone formation, localized areas of excessive bone resorption and formation

Lamellar is woven and wierd

Treated with bisphosphonates (also zoledronic acid)