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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by Quintal on August 3, 2007, at 23:31:14
I was struck down with terrible abdominal pain a few weeks ago so I went to my GP after a week of agony, suspecting gallstones. But after a brief examination it was apparent my gallbladder was fit as a fiddle. The dear lady, no doubt suspecting mischief on my part, was skeptical, but prescribed a months supply of the proton-pump inhibitor lansoprazole anyway (30mg in the morning) with instructions to make another appointment if the pain returned after the course was complete. The idea being to switch off the stomach acid and allow the ulcer to heal over for a month before switching the acid back on again.
Some people, such as my dad, take these drugs long term though and there is evidence of 'increased risk of hip fracture' (I'm assuming that's a polite way of saying they cause osteoporosis) in people taking them for a year or more.
__________________________________________________Long-term Proton Pump Inhibitor Therapy and Risk of Hip Fracture
Yu-Xiao Yang, MD, MSCE; James D. Lewis, MD, MSCE; Solomon Epstein, MD; David C. Metz, MD
JAMA. 2006;296:2947-2953.
Context Proton pump inhibitors (PPIs) may interfere with calcium absorption through induction of hypochlorhydria but they also may reduce bone resorption through inhibition of osteoclastic vacuolar proton pumps.
Objective To determine the association between PPI therapy and risk of hip fracture.
Design, Setting, and Patients A nested case-control study was conducted using the General Practice Research Database (1987-2003), which contains information on patients in the United Kingdom. The study cohort consisted of users of PPI therapy and nonusers of acid suppression drugs who were older than 50 years. Cases included all patients with an incident hip fracture. Controls were selected using incidence density sampling, matched for sex, index date, year of birth, and both calendar period and duration of up-to-standard follow-up before the index date. For comparison purposes, a similar nested case-control analysis for histamine 2 receptor antagonists was performed.
Main Outcome Measure The risk of hip fractures associated with PPI use.
Results There were 13 556 hip fracture cases and 135 386 controls. The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI therapy was 1.44 (95% confidence interval [CI], 1.30-1.59). The risk of hip fracture was significantly increased among patients prescribed long-term high-dose PPIs (AOR, 2.65; 95% CI, 1.80-3.90; P<.001). The strength of the association increased with increasing duration of PPI therapy (AOR for 1 year, 1.22 [95% CI, 1.15-1.30]; 2 years, 1.41 [95% CI, 1.28-1.56]; 3 years, 1.54 [95% CI, 1.37-1.73]; and 4 years, 1.59 [95% CI, 1.39-1.80]; P<.001 for all comparisons).
Conclusion Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.
Author Affiliations: Division of Gastroenterology (Drs Yang, Lewis, and Metz), Center for Clinical Epidemiology and Biostatistics (Drs Yang and Lewis), Department of Biostatistics and Epidemiology (Drs Yang and Lewis), and Division of Endocrinology (Dr Epstein), University of Pennsylvania School of Medicine, Philadelphia; and Department of Medicine, Doylestown Hospital Research Center, Doylestown, Pa (Dr Epstein).
__________________________________________________Q
Posted by Phillipa on August 4, 2007, at 12:27:36
In reply to Proton-pump Inhibitors and Bone Damage, posted by Quintal on August 3, 2007, at 23:31:14
Quintal you know I don't understand all the technical stuff but in essence does getting rid of stomach acid inhibit your ability to absorb calcium or I on a planet out in the universe somewhere? Love Phillipa
Posted by Quintal on August 4, 2007, at 17:19:06
In reply to Re: Proton-pump Inhibitors and Bone Damage » Quintal, posted by Phillipa on August 4, 2007, at 12:27:36
That's about right Phillipa. They're saying that low stomach acid may impair the absorption of calcium. They also say that proton pump inhibitors (PPIs) might interfere with bone resorbtion by inhibiting the proton pump of cells caled osteoclasts that break down bone. Osteoclats secrete hydrogen ions (basically hydrocholric acid) to dissolve bone minerals, and if their proton pump is inhibited this process cannot take place. This would seem to imply that bone mineral denisty actually increases during PPI treatment. I'm not sure why this would lead to brittle bones, although I have read reports from some bone specialists that say it's the collogen content of bone that's more important in preventing brittle bones, since collogen is flexible and acts as a shock absorber. Therefore a high mineral denisty combined with a low collogen denisty makes the bone hard and brittle, and PPIs may be tipping the mineral/collogen blanace in that direction.
There has been some correspondence between the authors of that study and a member of the Cedars-Sinai Medical Centre in Los Angeles in which Jordan L. Geller seems to imply that the results of this study may be due to 'the pandemic of vitamin D deficiency in adults'.
__________________________________________________
To the Editor: While secondary causes of osteoporosis frequently contribute to hip fractures,1-2 studies of these associations may be hampered by a lack of control for relevant confounding variables. In assessing the association of gastric acid suppression with hip fractures, Dr Yang and colleagues3 did not address vitamin D status as a potential confounder.
The authors hypothesize that gastric acid suppression may impair the release of ionized calcium from calcium salts, leading to calcium malabsorption and impaired skeletal mineralization. However, despite the pandemic of vitamin D insufficiency in adults,4 this vital component of bone health was not considered. There is an inverse relationship between serum 25-hydroxyvitamin D status and parathyroid hormone levels in patients with hip fractures.5 However, Yang et al3 did not provide data regarding the participants' vitamin D status, parathyroid hormone levels, or urinary calcium concentration.
Without these data, it is not clear whether the observed difference in . . . [Full Text of this Article]
Jordan L. Geller, MD
jordan.geller@cshs.org
John S. Adams, MD
Division of Endocrinology
Cedars-Sinai Medical Center
Los Angeles, Calif
__________________________________________________The authors disagree and reply:
__________________________________________________
In Reply: We disagree with the suggestion of Drs Geller and Adams that our observed association between PPI use and hip fracture may be confounded by the pandemic of vitamin D deficiency. By definition, a confounder must not only be associated with the disease of interest, it must also be associated with the exposure under study, and it must not be affected by the exposure or the disease.1 Geller and Adams support their concern about confounding of the association between gastric acid suppression and hip fractures by citing evidence of vitamin D status as a risk factor for hip fractures. However, by not considering how PPI therapy might relate to vitamin D status, they ignored 2 of the 3 essential elements that characterize a confounder.
We are not aware of any data that suggest that PPI use may cause or exacerbate vitamin D deficiency. Our search of the literature did . . . [Full Text of this Article]
http://jama.ama-assn.org/cgi/content/abstract/296/24/2947
__________________________________________________So as yet the mechanism behind the increased risk of hip fracture is unknown. This is worrying because if calcium absorption is affected it's likely that other minerals are too, and possibly many other nutrients. I think vitamin B12 deficiency has also been linked to low stomach acid, so PPI patients may be at risk of that as well. Clearly people receiving PPI therapy long-term are at risk of serious injury so why is more not being done to alert patients and doctors? My dad has noticed strong ridges on his fingernails of late, a sign of mineral deficiency, but we don't know the best course of action to take. Nor does his doctor.
Q
Posted by Honore on August 5, 2007, at 11:17:55
In reply to Proton-pump Inhibitors and Bone Damage, posted by Quintal on August 3, 2007, at 23:31:14
Wow. thanks for that information, Quintal. I'll keep that very much in mind.
Honore
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