Interesting article on possible side effects of Proton Pump Inhibitors

The_Conductor

Link here

Impaired gastric acidification affects calcium homeostasis and bone mass
By Anita Wilkinson
22 June 2009
Nature Med 2009; Advance online publication

MedWire News: A mouse study linking low gastric acid to calcium homeostasis and bone loss could impact on the treatment of many patients who receive proton pump inhibitors, researchers believe.

The team found that impaired gastric acidification affected calcium homeostasis, triggering hyperparathyroidism-induced bone loss.

Combining impaired gastric acidification with a bone-resorbing genetic defect called osteopetrosis led to impaired skeletal mineralization and early death from severe hypocalcemia.

The researchers say: “Given that both pathologies can be normalized by calcium supplementation in mouse models, we believe that our data are also of clinical relevance, not only for osteopetrotic patients but also for many individuals suffering from hypochlorhydria or receiving proton-pump inhibitors.”

Activation of osteoclasts and their acidification-dependent resorption of bone are thought to maintain proper serum calcium levels, say Michael Amling (University of Hamburg, Germany) and colleagues.

However, they found that osteoclast dysfunction alone did not generally affect calcium homeostasis. Mice deficient in Src, which encodes a tyrosine kinase critical for osteoclast activity, show signs of osteopetrosis but without hypocalcemia or defects in bone mineralization.

Animals deficient in Cckbr, encoding a gastrin receptor that affects parietal cell acid secretion, had predicted gastric acidification defects but also secondary hyperparathyroidism, osteoporosis, and modest hypocalcemia. The phenotype was fully rescued by calcium gluconate supplementation.

Mice deficient in Tcirg1, encoding a subunit of the vacuolar proton pump expressed in both osteoclasts and parietal cells, showed hypocalcemia and osteopetrorickets, in which there is rachitic widening of the growth plates.

Reporting in the journal Nature Medicine, the researchers say osteopetrosis and osteopetrorickets appear to be two distinct phenotypes depending on the site of defective acidification.

They add: “We believe that it will be important to treat osteoporotic patients who have hypochlorhydria or receive proton-pump inhibitors with calcium supplements that are soluble at neutral pH, such as calcium citrate or calcium gluconate.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

Free abstracts

The_Conductor

On the same topic here

Stomach acid-suppressing drugs linked to hip fracture risk
By Mark Cowen
19 June 2009
Digestive Disease Week; Chicago, Illinois, USA: 30 May–4 June 2009

MedWire News: Stomach acid-suppressing drugs called proton pump inhibitors and histamine-2 receptor antagonists are effective for the treatment of patients with gastro-oesophageal reflux disease and other digestive disorders, but they may be associated with an increased risk of hip fractures, say researchers.

A number of previous studies have suggested that stomach acid suppressing drugs may increase the risk of fractures, but others have found no such association, explained lead researcher Dr Douglas Corley, from Kaiser Permanente in San Francisco, California, USA.

To investigate further, Dr Corley and team studied data from the Northern California Kaiser Permanente integrated health-services organisation on 33,752 patients who suffered hip fractures and 130,471 similar patients who did not.

They assessed the patients’ use of proton pump inhibitors and histamine-2 receptor antagonists as well as confounding factors such as smoking, alcohol use and use of other medications.

The researchers found that patients who had suffered hip fractures were 30% more likely to have used proton pump inhibitors for at least 2 years and 18% more likely to have used histamine-2 receptor antagonists for at least 2 years than the other patients.

Overall, higher doses and longer durations of stomach acid-suppressing treatment were associated with corresponding increases in fracture risk. Indeed, compared with patients who had never taken stomach acid suppressing drugs, those who had taken more than one pill a day for at least 2 years had a 41% increased risk of fractures, those who had taken one pill a day for at least 2 years had a 30% increased risk and those who had taken less than one pill a day had a 12% increased risk.

The team also noted an increased risk of hip fractures among patients who had used stomach acid-suppressing drugs for shorter periods of time.

“Although we cannot exclude persistent confounding, the increased risk with short-term use of acid suppressing drugs suggests that even relatively brief periods of use may be associated with increased risk of hip fractures,” said Dr Corley.

Speaking at Digestive Disease Week 2009 in Chicago, Illinois, USA, he concluded: “Patients taking acid suppressors should continue treatment at the lowest effective dose. However, they should discuss treatment options with their doctor if they are at risk of osteoporosis.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

Free abstract

DrIndy

This is very interesting indeed - please repost it in Bio/Med - its potentially a huge issue.

RobFowl

PPI's are the most precribed grugs both here and in the UK !

drzhivago

RobFowl wrote: »

PPI's are the most precribed grugs both here and in the UK !

are they available over counter as well in low dose

RobFowl

drzhivago wrote: »

are they available over counter as well in low dose

They are to an extent in the UK but not here.

drzhivago

RobFowl wrote: »

They are to an extent in the UK but not here.

sorry for using trade names Zantac a H2 blocker is I thought LOSEC PPI was as well

Nonoperational

Have you guys seen a study about PPIs reducing the efficacy of clopidogrel? Protium and to a lesser extent nexium seem to be exculded but the others appear to affect significantly the its metabolism and bioavailability.