Rheum E1 -Metabolic & Hormonal diseases

Which has priority of calcium: serum or bone?

Serum

What is Calcium essential for?

muscle contraction, nerve function, blood clotting, etc

What is Osteomalacia?

Bone softening from excessive resorption of Ca from extracellular bone matrix and/or lack of vitamin D

Bone contains ___% of calcium in the body

99%

What decreases Calcium absorption?

low levels of vit D, diet low in Ca, GI disease (malabsorption), diets high in phosphates, phytates, oxalates, & heavy metals

How is the majority of Calcium excreted?

bowels

Daily calcium requirements - child

800-1,000 mg

Daily calcium requirements - adult

1,000-1,200 mg

Daily calcium requirements -pregnancy, peri/post menopausal, pts w/ fxs

1,500 mg

Daily calcium requirements - breast feeding

2,000 mg

Daily calcium requirements - adolescents (growth)

1,000-1,300

Where is the majority of Phosphate excreted?

kidney

What is the daily phosphate requirement?

800-1,200 mg

PTH favors (osteoblasts/osteoclasts)

Osteoclasts

PTH causes Ca & PO4 to move into the (serum/bone)

Serum

What is the primary regulator of extracellular calcium that is released in response to low serum calcium?

PTH

What is the action of osteocytes in rapid response to hypocalcemia?

Release Ca stored in lacunar spaces

What effect does PTH have on the kidney?

PO4 diuresis, Resorption of Ca, Make activated Vit. D

What effect does PTH have on the gut?

Increased permeability to Ca by stimulating kidney to make Vit. D

What does the liver metabolize vitamin D into?

25(OH) Vitamin D2 (storage levels)

The kidney metabolizes 25(OH) Vitamin D2 into ___________ or ____________

Cholecalciferol or Ergocalciferol

Which is more potent/active: Cholecalciferol or Ergocalciferol

Cholecalciferol

Where is calcitonin secreted from?

Thyroid (C cells)

Calcitonin inhibits (osteoblasts/osteoclasts)

Osteoclasts

How does insulin affect bone metabolism?

helps w/ bone mineralization, skeletal growth, bone remodeling

What is the effect of insufficient GH?

dwarfism

What is the result of excessive GH?

gigantism or acromegaly

Which is necessary for bone formation and inadequate amounts results in bone loss?

Estrogen

What is the effect of excess glucocorticoids?

impaired skeletal growth, dec bone formation & bone mass

What is the MC form of osteoporosis?

Primary, Type I (postmenopausal)

Which form of Osteoporosis is due to senescence?

Primary, Type II (senile)

What type of Osteoporosis is due to disease, genetics, drugs, etc.?

Secondary

What are risk factors for an Osteoporotic fx?

Caucasian/Asian, postmenopausal, hx of fx, low body wt, current smoking, ETOH, old age, use of corticosteroids of 7.5mg for 3+ months

What are the significant RF for men for Osteoporosis?

undx low testosterone levels, declining testosterone AND estrogen levels w/ age, ETOH, smoking

What is the MC type of fx associated with osteoporosis?

Vertebral

What medical conditions increase risk for osteoporosis?

insulin-dependent DM, malabsorption syndromes, RA, IBS, hyperparathyroidism, hypogonadism

What drugs reduce bone mass in adults?

glucocorticoids, adrenocorticotropin, anticonvulsants, blood thinners, cytotoxic drugs, Depo-provera, thyroid suppression

What is the most serious consequence of osteoporosis?

Hip fx

What is the Gold standard diagnostic test to detect osteoporosis?

Bone mineral density or DEXA

What diagnostic study can be used in osteoporosis to predict chances of future fx?

FRAX

What diagnostic study can be used in osteoporosis to assess rate of bone loss and/or monitor effects of treatment?

Bone turnover markers

Normal BMD T-score:

> -1.0 SD

Low BMD T-score (osteopenia):

Between -1.0 and -2.5 SDs

BMD T-score for osteoporosis:

-2.5 or lower

At what age should all women have a BMD test?

65+

At what age should all men age have a BMD test?

70+

When should a BMD test be done regardless of age?

presence of fragility fxs (hip, vertebral), loss of ht > 1.5 in, younger women/men w/ 1+ RF

Where does the FRAX measure BMD at?

femoral neck

What does the FRAX predict?

10 yr probability of overall skeletal fx (>20%) and hip fx (>3%) as high risk in pts

T/F: Bone turnover markers are NOT recommended for diagnosis of osteoporosis

True- they are recommended for monitoring of tx

What can help lower risk of Osteoporosis?

adequate intake of Ca & vit D, wt/resistance training, avoid tobacco and excessive alcohol, strategies for fall prevention

Which vitamin is essential for absorption of Ca from the GI tract?

vit D

What medication is 1st line prevention/tx for osteoporosis?

Bisphosphonates

(-dronate, -dronic)

What medications for Osteoporosis are anti-resorptives?

Estrogen/HRT, Bisphosphonates, SERMS, Calcitonin, Denosumba (prolia)

What medications for Osteoporosis are anabolics?

PTH, PTHrP analogue, Romosozumab (-mabs)

Which class of osteoporosis medications cause apoptosis of osteoclasts?

Bisphosphonates

What are the SE of bisphosphonates?

*these are uncommon!

Irritation/burning of esophagus, abd/msk pain, nausea, osteonecrosis, pathologic fxs w/ long term use

What medication is used as a last resort for osteoporosis?

*when pts cannot tolerate other meds

Calcitonin (Miacalcin)

What are adverse effects of Calcitonin?

nasal irritation, backache, bloody nose, HA

Which SERM medication is approved for prevention & treatment of postmenopausal osteoporosis?

Raloxifene (Evista)

What are adverse effects of Raloxifene (Evista)?

Hot flashes, DVT, Leg cramps

Which Osteoporosis medication is an anabolic agent that up-regulates osteoblasts?

PTH, Teriparatide (Forteo), Abaloparatide (Tymlos)

Which osteoporosis medications have a black-box warning for osteosarcoma findings in animals?

*so far none reported in humans

PTH, Teriparatide (Forteo), Abaloparatide (Tymlos)

What are SE of PTH medications?

nausea, leg cramps, dizziness

PTH medication is limited to use of ____

2 yrs

Which Osteoporosis medication acts as a RANKL inhibitor?

Denosumab (Prolia)

Which -MAB binds sclerostin, blocking the Wynt pathway resulting in up-regulation of osteoblasts?

Romosozumab (Evenity)

Which osteoporosis medication has a black box warning for CV disease, such as stroke/MI, thrombosis, and death?

Romosozumab (Evenity)

What is Paget's disease?

excessive bone resorption and formation with abnormal remodeling of bone → weak, deformed, enlarged, vascularized (woven bone)

Paget's disease commonly affects what demographic?

M > F, 50+ (inc in those 65-74)

What is a complication of Paget’s?

osteosarcoma risk

What are the cardinal features of Paget's disease?

Enlarged skull, Tinnitus, Bowed legs

What are the 1st line tests for dx Paget's disease?

Elevated serum alkaline phosphatase, Plain films

What would you see on an Xray of Paget's disease?

abn skeletal survey: "Salt and pepper" pattern

What dx test determines the extent of bone involvement in Paget’s?

total body bone scan

What is the 1st line/main treatment for Paget's disease?

Bisphosphonates (alendronate)

Calcium is stored as ________ embedded in & on the collagen fibers of bone

Hydroxyapatite crystals

What facilitates the absorption of calcium?

PTH & Vitamin D

Phosphate absorption is (increased/decreased) by a low calcium diet or high levels of vitamin D

Increased

If PTH stimulus continues, ______ are signaled to resorb bone

Osteoclasts

What serum level test is the test of choice to determine in a patient is vitamin D deficient?

25(OH) vitamin D2

What is the biologically active form of vitamin D?

Calcitriol

What is the MOA of Anti-resorptive agents?

Kill osteoclasts

What is the MOA of anabolic agents?

Upregulate osteoblasts

What is the main function of sclerostin?

Stop (inhibit) bone formation