Long term proton pump inhibitor use

Many adults born with OA/TOF have been on PPI for many years, and some since their inception in the 1980s. These adults may approach the GP to discuss concerns about side-effects of long-term use of PPIs, which, whilst certainly present, need weighing against the risks of possible lifelong untreated acid reflux disease.

Risks of untreated acid reflux/GORD

• Oesophageal ulcers
• Oesophageal haemorrhage
• Anaemia secondary to chronic blood loss from oesophagitis
• Oesophageal strictures
• Barratt’s oesophagus
• Oesophageal cancer

Long-term side effects of PPIs

• Increased fracture/osteoporosis risk. There are several reasons to suspect PPIs might be associated with fractures. The most plausible theory is that a decrease in stomach acid production might reduce calcium absorption in the small intestine. Over a long period, this could be followed by a decrease in bone mineral density. This mechanism remains largely theoretical and several studies have failed to show any reduction in bone mineral density in adults taking PPIs. Bone mineral density and fractures in adults and children taking PPIs long term has been (and still is) the subject of a large number of studies. The results are conflicting. The main problem with all these studies is that people who take PPIs are likely to be older and sicker than people who don’t. People who are old and frail have other risk factors for fractures that are far more important than PPIs. Nearly all of the published studies have tried to correct for this confounding effect but it is difficult to eliminate completely. (36,87) However, NICE advises careful monitoring for osteoporosis and risk of fracture in those at higher risk and on PPIs, and prescription of calcium and vitamin D supplementation if needed. This should be considered in the context of poor nutritional status in some born with OA/TOF. (88)
• Here again, evidence is conflicting, and falls foul of the same issues that the fracture risk studies do, that the participants in studies taking PPIs will be older and sicker than those who don’t.
• Clostridium difficile infection. Acid in the GI tract reduces susceptibility to this infection so high-dose PPI use is associated with increased numbers of this infection. (89)
• Hypomagnesemia (magnesium deficiency), B12 deficiency. NICE recommends checking magnesium levels before and intermittently during PPI treatment if other factors are present that increase risk of hypomagnesemia. (88)
• Anaemia due to PPIs reducing iron absorption. (90)
• Increase in gastric neuroendocrine tumours (GNETs). This is a very rare malignancy, but one has occurred in an Adult TOF who has been on high dose PPIs for 20+ years. However, these are indolent tumours and, unlike their non-PPI-induced counterparts, are usually superficial lesions which are easily removed. (91) It is impossible to compare the risk of oesophageal malignancy and GNETs in adults born with OA/TOF, but the limited research and our knowledge of these two malignancies would suggest that it is better to prevent a much higher risk of Barratt’s oesophagus and the risk of oesophageal cancer if left untreated, as this is a much more aggressive and difficult to manage malignancy, than to avoid PPIs for a miniscule risk of a rarer and better prognosis GNET.

Intermittent monitoring of iron, magnesium, B12, Vitamin D is recommended for those on long-term PPIs as those with OA/TOF may have other causes of malabsorption. Assessment of osteoporosis risk is also recommended. (92)