Question in UWORLD about mechanism of PPIs causing Hip Fracture

[britesky89]

Hi guys, there was a question in UWORLD about how omeprazole increases the risk of hip fracture.

"65 yo F; mother has a Hx of hip fracture for which she was recently hospitalized, causing her to be concerned about her own risk for hip fracture. She has a Hx of HTN, hyperlipidemia, CAD, GERD, & migraine. She has a 30 year smoking Hx of one pack daily for 24 years, but does not consume alcohol. She had menopause at age 52. She walks her dog for a mile almost everyday and has no trouble with keeping her balance or falling. Long term use of which drug would increase her risk of fracture?
A. Atorvastatin
B. Chlorthalidone
C. Metaprolol
D. Nitroglycerin
E. Omeprazole (CORRECT ANSWER)
F. Topiramate

In the explanation it says that PPIs decrease calcium absorption because insoluble calcium (calcium carbonate) requires and acidic environment for proper absorption, and PPIs, by suppressing acid, interfere with this.

What I'm confused about is don't osteoblasts require an ALKALINE environment for their action? After all they use ALP?

Plus, in first aid under the topic of osteopetrosis, it says that osteoclasts require an ACIDIC environment for bone resorption.

So, by inhibiting the acidic environment, doesn't that allow for better bone re absorption?

Any clarification would be appreciated!

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[dfib slim]

Osteoclasts use proton pumps to create the acidic environment needed for bone resorption. By inhibition of these proton pumps by PPIs there will be less bone resorption and an increase risk for fractures.

 

[britesky89]

Osteoclasts use proton pumps to create the acidic environment needed for bone resorption. By inhibition of these proton pumps by PPIs there will be less bone resorption and an increase risk for fractures.

Doesn't Less bone resorption Decrease the risk for fracture? If there's less bone resorption then there must be more bone formation right? Maybe I'm not understanding the exact meaning of resorption?

 

[dfib slim]

Doesn't Less bone resorption Decrease the risk for fracture? If there's less bone resorption then there must be more bone formation right? Maybe I'm not understanding the exact meaning of resorption?

Bone remodeling is a continuous process of resorption of old bone and replacement of new bone by osteoclasts/osteoblasts. Less resorption will leave the weakened bone and prevent the formation of new stronger bone in it's place.

http://cjasn.asnjournals.org/content/3/Supplement_3/S131.full

 

[blackcadillacs]

I think you are thinking of two different processes.

Yes, osteoblasts in the bone require an alkaline environment, but PPIs create an alkaline environment in the gut, where Ca absorption occurs. This creates a less favorable environment for Ca absorption, again in the gut. As far as I'm aware, PPIs have no effect on the acidity of bone.

Without proper Ca absorption in the gut, there won't be enough Ca to lay down bone.

 

[britesky89]

I think you are thinking of two different processes.

Yes, osteoblasts in the bone require an alkaline environment, but PPIs create an alkaline environment in the gut, where Ca absorption occurs. This creates a less favorable environment for Ca absorption, again in the gut. As far as I'm aware, PPIs have no effect on the acidity of bone.

Without proper Ca absorption in the gut, there won't be enough Ca to lay down bone.

Thank you for clearing that up! That was indeed what I was getting confused with. So now I understand that calcium absorption in the gut is different from the same process in the bone.

Also, I just looked through first aid again realized another correlation.

Under calcium homeostasis and it says "increased pH (alkaline) -> increases the affinity of albumin (negative charge) to bind calcium 2+ -> leading to clinical manifestations of hypocalcemia"

Less calcium, means less calcium to lay down bone, like you said.

Thanks a lot!