Term
| Where is calcium found in the body? |
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Definition
In the bones and teeth
Protein bound to albumin, complexed (citrate), or majority is ionized |
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Term
| What hormones/compounds regulate calcium? |
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Definition
- PTH - Promotes bone resorption when calcium is low. Promotes Ca reabsorption and phosphate excretion, formation of calcitriol
- Vit D - Increased GI absorption of calcium, renal reabsorption. Works with PTH
- Calcitonin - counteracts PTH. When calcium is HIGH - storage in bones or excretion. |
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Term
| What is calcitonin secreted by? |
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Definition
| Parafollicular cells of the thyroid |
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Term
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Definition
| Parathyroid gland(s) on the back of the thyroid, specifically chief cells |
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Term
| Is calcium absorption efficient? |
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Definition
No, 90% lost through fecal excretion.
But, the kidney can reabsorb calcium based on PTH levels and Ca levels. |
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Term
| What cells affect bones and calcium? |
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Definition
Osteoblasts - mineralize/build bone
Osteroclasts - demineralize bone
PTH low - kidneys excrete calcium and osteoblasts mineralize bone
PTH high - Kidneys reabsorb and osteoclasts demineralize bone. |
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Term
| How is phosphate dealt with in the body? |
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Definition
80% in bone, key regulator of energy
Absorption is Vit D dependent
** In bone - complexed w/ calcium to form hydroxyapatite crystals |
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Term
| What is the function of PTH? |
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Definition
Maintain plasma calcium and phosphate levels by:
- increasing bone resorption to mobilize calcium, excrete phosphate
- Acts via GPCRs: PTHR1 and 2.
** Intermittent activity: Osteoblasts. The MoA of Teriparatide/Forteo
** Chronic activity: osteoclasts |
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Term
| What is the MoA of Teriperatide/Forteo? |
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Definition
Intermittant action of PTH - stimulate osteoblasts
human PTH fragment. |
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Term
| How does the body tell when it needs calcium? |
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Definition
Calcium sensing receptor senses calcium levels. Increased calcium --> PKC pathway and PTH inhibition.
** Low calcium --> PKA pathway and PTH activation. Osteoclasts, Ca reabsorption, Pi excretion. Vit D activates. |
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Term
| How is osteoclast activity mediated? |
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Definition
Binding of RANKL to RANK --> Osteoclast activation. PTH increases RANKL, decr OPG
**OPG inhibits RANKL. If RANKL is inhibited, so are osteoclasts. |
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Term
| How does PTH reabsorb calcium renally? |
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Definition
| Upregulates calcium channels in the lumen. Calcium binds to calbindin --> diffusion. Transport out of cell by Na/Ca antiporter and Ca-atpase |
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Term
| What role does Vit D play with calcium? |
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Definition
UV converts to calcitriol. Calcitriol augments absorption of calcium and phosphate
- Works w/ PTH to reduce renal excretion.
**Ca decreases --> surge in D3
**Enhanced calcium reabsorption in the intestine |
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Term
| What is the role of calcitonin in calcium regulation? |
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Definition
When calcium is high, brings calcium down. Action opposes PTH.
Binds to and inhibits osteoclasts.
Blocks renal reabsorption of calcium --> excretion |
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Term
| What drugs are Vit D analogues? |
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Definition
- Calcitriol/Calcijex or Rocaltrol. - active
- Doxyercalciferol/Hectorol - a prodrug, activated by hydroxylation
- Dihydrotachysterol/Roxane - reduced vD2, converted by the liver
- 1OHD/One Alpha - already hydroxylated, hepatically activated |
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Term
| What do Vit D analogues require for activity? |
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Definition
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Term
| How does a decrease in estrogen affect bones? |
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Definition
Increased bone resorption, decreased formation. ERalpha mediated.
Low blood Ca triggers catabolism. |
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Term
| What is the med-chem of bisphosphonates? |
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Definition
All have a P-C-P backbone that can chelate cations such as calcium: affinity for bone surfaces.
**2nd gen contains nitrogen: Inhibits FPPS, farnesol, geranylgeraniol required for prenylation. |
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Term
| What is the MoA of bisphosphonates? |
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Definition
Inhibit osteoclast formation - induce apoptosis
Limit bone turnover, allowing osteoBLASTS to form.
2nd gen - inhibition of cholesterol pathway |
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Term
| What are 1st generation bisphosphonates? |
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Definition
- Etidronate/Didronel
- Tiludronate/Skelid
**Used for Paget's disease |
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Term
| What are 2nd generation bisphosphonates? |
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Definition
- Pamidrone/Aredia
- Alendronate/Fosamax
- Ibandronate/Boniva
**Along with inducing apoptosis, inhibits prenylation necessary for osteoclast proliferation.
HIGH affinity for hydroxyapatite crystals |
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Term
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Definition
| Incorporation of a farnesyl or geranylgeraniol - long fatty acids - into a GPCR |
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Term
| How do bisphosphonates induce apoptosis? |
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Definition
| Inhibition of FPP synthase --> Isopentanyl pyrophosphate precursor builds up --> APPPL, which is toxic to osteoclasts. |
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Term
| What are 3rd generation bisphosphonates? |
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Definition
- Risendronate/Actonel
- Zolendronate/Reclast
**Aryl rings w/ Nitrogen. Can be renally toxic. |
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Term
| What are bisphosphonate considerations? |
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Definition
- All are poorly bioavailable, better w/ generation
- DO NOT TAKE W/ FOOD. Drink with non-mineral water. Separate from other medications.
- Excreted by kidneys
- Causes heartburn --> remain upright.
- ONJ with some agents |
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Term
| What is Raloxifene/Evista? |
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Definition
A SERM, analogue of tamoxifen.
Agonist at bone/CV
Antagonist at breast and uterus
**Decreased resorption, increased BMD, decreased fracture risk. |
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Term
| What are the steps of bone remodeling? |
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Definition
1) Activation - pre-osteoclasts stimulated to mature
2) Resorption - Digestion of old bone
3) Reversal - end of resorption
4) Formation - Synthesis of new matrix
5) Quiescence - Blasts become bone lining on new surface |
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Term
| What do vertebral fractures lead to? |
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Definition
- Kyphosis - outward curvature of thoracic region
- Lordosis - forward curvature of lumbar and cervical regions |
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Term
| What are the classifications of OP? |
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Definition
- Primary - age related or post-menopausal
- Secondary - due to medical disorders or medication |
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Term
| What are MAJOR risk factors for OP? |
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Definition
Modifiable: Smoking, low BMI, low BMD
Non-modifiable: Female, short, white/asian, advanced age |
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Term
| What is the most common medication that causes OP? |
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Definition
| Glucocorticoids: Steroids > 5 mg/day for 3 months. |
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Term
| What are risk factors for falls? |
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Definition
Medical: H/x, weakness, poor vision, dehydration, dementia, sedating medication
Environmental: Lack of assistance, poor lighting, obstacles |
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Term
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Definition
A T-score - mean SDV from young adult female.
- normal - -1.0 and above
- osteopenia - -1.0 to -2.5
- osteoporosis - -2.5 or below.
**can only use this on post-menopausal women |
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Term
| Who is indicated for BMD scanning? |
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Definition
- Women > 65
- Men > 70
- Adults at risk for fracture
**FRAX - 10 year probability of hip fracture for post-menopausal women |
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Term
| What can be done to prevent OP? |
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Definition
- Limit caffeine and sodium
- Limit alcohol, stop smoking
- Avoid low-protein
- Calcium essential for prevention and Tx |
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Term
| What is the clinical presentation of OP? |
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Definition
- T score of -2.5 or below
- Hip or vertebral fracture
- Height loss |
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