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Isolated Alk Phos Elevation

Paul Simmons, MD
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How many times have you ordered a CMP as part of a routine lab work up, and encountered an elevated alkaline phosphatase? If your next question is, “what now?”, you’ll appreciate Dr. Paul Simmons sharing his tips for the work up of this common finding.

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Rose W., PAC -

How does osteoporosis and taking bisphosphonate effect ALK PHOS

Neda F., MD -

Hello, Rose:

Thanks for your question! I found a couple of studies that addressed this question and reinforced my own pathophysiologic reasoning on your question:

Osteoporosis IS associated (not perfectly - sensitivity in the 70s, specificity in the 80s) with high alkaline phosphatase levels. This makes sense because of the shift with menopause toward osteoCLAST activity leading to bone matrix breakdown and, therefore, release of alkaline phosphatase into the blood. Conversely, bisphosphonates INHIBIT osteoclasts, shifting the balance of power back toward bone formation (or at least less breakdown), so alkaline phosphatase levels should normalize with bisphosphonates.

Pretty cool, eh?

Paul Simmons

Rose W., PAC -

Am I disregarding isolated alkphos that are not 》 1.5 x normal limit?

Neda F., MD -

Hello, Rose:

Thanks for your question!

According to my reading, a mildly elevated alkaline phosphatase should only be disregarded AFTER a limited evaluation (GGT to confirm a hepatic source, AST/ALT to rule out hepatocellular injury, and maybe a RUQ U/S) is NEGATIVE. Then, you can observe a mildly elevated alkaline phosphatase according to the algorithms I've seen.

That being said, there's some clinical judgement here, obviously: If the patient's had a recent fracture - likely a bone source, I'd observe. Patient has type O or B blood? Likely a hereditary thing - I'd observe. And so on... I think you have to try to put the alkaline phosphatase into the clinical context and see if you can explain it. If not, I'd do the workup because it can be an early sign of either a hepatocellular, biliary or bone problem.

Hope that helps!

PDS

Stephen L., 7886654 -

There was a nice paper in the BMJ a few years ago that had a good algorithm and approach that I recommend. See the link below. Enjoy!

Shipman, Holt & Gama (2013) Shipman KE, Holt AD, Gama R. Interpreting an isolated raised serum alkaline phosphatase level in an asymptomatic patient. BMJ: British Medical Journal. 2013;346 doi: 10.1136/bmj.f976. Article f976.

Pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/23553977

Neda F., MD -

Thanks so much, Stephen! We love this sort of thing! -- Neda

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Primary Care RAP December 2019 Written Summary 3 MB - PDF

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