Premature discard of proton pump inhibitors: possible osteoporosis vs enhanced gastrointestinal bleed, adenocarcinoma efficacy.

To the Editor: I commend Davidge Pitts and Kearns1 for alerting clinicians to the detrimental osteoporotic effects of newer pharmaceuticals that clinicians initiate but fail to reevaluate. However, I encourage clinicians to use considerable caution before accepting the authors' premature endorsement of substituting H2 receptor blockers (H2RBs) for proton pump inhibitors (PPIs). Millions of people ingest nonsteroidal anti-inflammatory drugs (NSAIDs) long term. The demographics of osteoporosis are inordinately concordant with the elderly population as well as with long-term NSAID consumption (with NSAID use related to the treatment of osteoarthritis pain, and aspirin prophylaxis for ischemic events). The thinned gastric mucosa in the elderly enhances their susceptibility to severe NSAID-induced adverse events. Proton pump inhibitors do not simply block histamine receptor–mediated gastric parietal cell acid secretion effected by H2RBs. Proton pump inhibitors terminate the final stage of acid production, and they also block parasympathetic vagus nerve–mediated acetylcholine neurotransmitter and gastrin hormone stimulation of parietal acid production, constituting a substantial improvement over H2RBs. Additionally, PPIs are more efficacious than H2RBs in reducing risk of gastroduodenal ulcers,2 and, as such, they are superior in mitigating mortality risks for thousands of patients who annually experience NSAID-induced gastrointestinal bleeds (GIBs) and tens of thousands of patients who experience nonfatal hospitalization–related morbidity due to GIBs. Similarly, PPIs are superior to H2RBs in the minimization of gastroesophageal reflux symptoms, premalignant Barrett metaplasia, dysplasia, and esophageal adenocarcinoma. Only with supraphysiologic dosing can H2RBs approximate PPI potency, but such dosing is accompanied by adverse cognitive effects in the elderly and potentiates the risk of induced falls, often a preterminal cascade event. The fewer adverse events associated with PPIs must be considered relative to a recent prospective analysis of 161,806 postmenopausal women aged 50 to 79 years. This research identified that PPIs were not associated with hip fractures and only modestly associated with spine, forearm, wrist, or total fractures.3 The study concluded that “hip fractures were so rare” that long-term use of PPIs “made no difference” in their analysis.4 Conflicting data regarding validity of PPI use and fracture risk must be contrasted to studies reporting that H2RB acid suppression also induces osteoporosis with hip fractures.5 Davidge Pitts and Kearns1 reported that thiazolidinediones compromise bone quality “in men concomitantly taking loop diuretics.” Loop diuretics promote loss of total body calcium in the urine, whereas thiazides are calcium-sparing. Future studies assessing the merit of endorsing H2RBs substituted for PPIs (eg, in terms of bone loss) must control better for confounding factors such as diuretic selection. This is a prerequisite if we are to establish or refute the legitimacy of whether PPIs contribute to fracture risk. A precipitous resumption of H2RBs with discard of the pharmacologic advancement of PPIs is currently unwarranted. Until higher-quality evidence regarding bone and H2RB use is established relative to the use of PPIs and these outcomes are correlated with GIBs, reflux, and fall risks, clinicians should continue favoring PPIs. However, given the evidence reported by Davidge Pitts and Kearns, cautious responsive addition of bone-enhancing strategies with calcium supplements, vitamin D, pharmaceuticals, cautious loop diuretic substitution for thiazides, and diagnostic investigation to identify contributors to impaired bone quality will optimize care for patients continuing to ingest PPIs long term.