Calcium (Hockerman) Flashcards
what is the term fr moving both phosphorus and Ca2+ in and out of bone?
continuous balance
what ARE OSTEOBLASTS?
bone forming cells
what are osteoclasts?
bone reabsorption cells
what inc. BMD?
- osteonectin
- nitric oxide
- denin matrix protein 1
what dec. BMD?
- sclerostin
- DKK-1
- RANKL
what does a deletion of aa in the PTH do?
deletion aa 1&2 eliminates activity
what does PTH do?
- increase calcium in extracellular fluid
- inc. Ca2+ reabsorption from ECaC1 7 TrpV5
- inc. Ca2+ resorption from bone (inc. osetoclast # & activity)
- increased PO4 loss in urine
- inc. 1,25 (OH2) D3 production by kidney
- PTH secretion triggered by low serum Ca++ levels and GPCR that binds Ca2+ (CSR)
how can vitamin D (cholecalciferol) be obtained?
in the diet or via exposure to sun light
what does increased Ca2+ and PO43- absorption from small intestine do?
direct (rapid) effect on brush border of intestinal mucosal cells
what cells are there a indirect slow effect?
- calbindins
- vitamin D binding protein
what vitamin D deals with feedback inhibition of PTH?
1,25(OH)2D3
what does the fibroblast growth factor 23 do?
- auto/paracrine effect on osteocytes inhibits bone mineralization
- high levels of FGF23 correlate with poor prognosis in patients with CKD on dialysis
what do high Ca2+, 1,25(OH2) vit D3, and FGF23 inhibit?
PTH secretion
what does low Ca2+ do?
stimulates PTH secretion
what does a negative regulator of serum (extracellular) Ca2+ do?
- inhibit osteoclastic bone resorption
- increase Ca2+ and PO4 loss in urine
- stimulated by high serum calcium levels
what are some side effects of Padgetts disease?
- bone remodeling
- bone deformities
- loss of hearing, hypercalcemia
- may be caused by slowly acting virus
what are some risk factors for osteoporosis?
- physical inactivity
- age
- low Ca2+ intake in early years
- long term glucocorticoid therapy
what is hyperparathyroidism?
- inc. bone resorption and decreased Ca2+ excretion
what care some reasons for malignant tumors?
some produce a peptide with PTH activity
what are osme causes of CNS symtpoms?
depression and coma
what is a first line treatment for osteoporosis?
bisphosphates/ denosumab
what drugs for osteoporosis cause a high fracture risk?
teriparatide abaloparatide, romosozumab
what is a regimen for Vitamin D in osteoporosis?
- Vitamin D (800-1000 IU) + Ca2+ (>1200mg) daily can reduce fracture risk
- also supplement for osteoporosis therapy
what are the characteristics of bisphosphates?
- inhibit bone resorption
- 50% absorbed dose ends up in bone
- may lead to hypocalemia so we need to supplement with Ca2+ + Vit D
what bisphosphates are approved for padget’s and cancer but not for osteoporosis?
- pamidronate
- etidronate
what bisphosphates are approved for osteoporosis and build bone mass?
- zoledronate
- alendronate
- risendronate
- ibandronate
what is the mechanism of action of bisphosphates?
it disrupts prenylation of proteins in osteoclasts
what is teriparatide?
amino acid 1-34 of PTH produced in E.coli
what is abaloparatide?
amino acids 1-34 of PTHrP produced synthetically
where are PTH1 receptors expressed?
on osteoblasts and kidney cells
what does intermittent PTH do?
increase bone mass and strength
what does continuous PTH do?
increase bone resorption
what are the pros of teriparatide to bisphosphates?
build bone mass at higher rate than bisphosphonates
what are the cons of teriparatide to bisphosphates?
black box warning required by FDA for risk of bone cancer
–> reserved for severe cases of osteoporosis
tell me about prolia (denosumab)?
approved in June 2010 for postmenopausal osteoporosis
1. hypocalcemia risk- take calcium daily
2. increased risk of fracture upon discontinuation
tell me about romosozumab?
- MAB against sclerostin
- osteocyte secretion increased
- sclerostoin decreases osteoblasts and increases osteoclasts
- ADRs–> MACE (hypersensitivity, hypocalcemia, osteonecrosis, atypical fractures)
what is calcitonin and its characteristics?
- decreased osteoclast activity, blocks renal reabsorption of PO4 and Ca2+
- rapid loss of efficacy in treatment of hypercalcemia
- not the drug of choice in most causes for treatment of osteoporosis
what is the mechanism cinacalcet?
- CKD with dialysis the CSR become less responsive to Ca 2+
- cinacalcet is a PAM
- when cinacalcet is bound its more responsive to Ca2+
what are the characteristics for the second line treatment for hyperparathyroidism?
- Zemplar
–> stage 2&4 or dialysis
–> 1-4ug 3x per week IV or oral - Hectorol
–> dialysis
–> 4ug 3x per week IV or oral
–> prodrug- 25 hydroxylation by CYP 27 in live
» inhibit secretion of PTH with less effect on serum Ca2+ than 1,25(OH)2 Vit D3
what is the treatment of hyperphosphatemia in CKD with dialysis?
- calcification –> calcific uremic arteriolopathy
- phosphate binders are complex with dietary phosphate and prevent absorption from GI
- Sevelamer dec. serum PO43- levels selectively
- Lanthanum Carbonate dec. serum PO43- AND Ca2+ levels
what does calcium receptor sensitization do?
—decrease both serum PTH and Ca2+ levels and can help in
—many treatments such as chronic kidney disease with dialysis
what are third line treatments for osteoporosis?
estrogens/ SERMs
–> inc. osteoblasts and dec. osteoclasts
–> risk of blood clots
–> raloxifene& bazedoxifene
—–> antagonist: in breast/ uterus/ brain
——> agonist: in bone/liver
