This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
While a reasonable amount of “pumping iron” exercise has proven beneficial for musculoskeletal health, long-term use of acid-suppressing proton pump inhibitors (PPIs) may have the opposite effect on bone. Many people are currently taking PPIs, most commonly for gastrointestinal disorders such as heartburn and gastroesophageal reflux. Fortunately, many are occasional PPI users, taking the drugs only when symptoms arise. However, PPIs are often prescribed long term for preventive reasons.1
The same proton-pump mechanism present in the GI tract is seen in the vacuolar H+-ATPases that are present in high concentrations on the ruffled border of osteoclasts.2 Years of PPI use may therefore interfere with normal and essential bone remodeling. PPIs are also prescribed in the pediatric population for reflux symptoms. The effect of PPIs on future fracture or long-term osteoporosis in these very young patients is not clear.
The consequences for adult and elderly patients are clearer. Femoral bone mineral density is significantly decreased in PPI users. Also, patients with peptic ulcer disease using PPIs have a higher risk for osteoporosis than peptic ulcer patients not using PPIs. Among younger adults, the risk of fracture was significantly higher in those using PPIs than in those not using PPIs.
In 2010, the FDA issued a communication alerting healthcare professionals that users of PPIs have a possible increased risk of fractures of the hip, wrist, and spine, and that they should weigh the known benefits against the potential risks when recommending use of these medications. In 2011, the FDA refined its language somewhat: “Following a thorough review of available safety data, FDA has concluded that fracture risk with short-term, low dose PPI use is unlikely.” Still, when fractures are the outcome of interest, the data implicates long-term use of PPIs in having deleterious effects on bone.
Although data on human fracture healing in association with PPI use are sparse, animal studies do show that PPIs have a negative impact on normal fracture healing, with a decrease in the expression of important markers of bone formation, including bone morphogenetic protein (BMP)-2, BMP-4, and cysteine-rich angiogenic inducer (CYR)61.
It is time to question the need for chronic use of PPIs by our patients. Orthopaedists should encourage their patients who take PPIs to discuss this matter with their primary care physician.
- Eom CS, Park SM, Myung SK, Yun JM, Ahn JS. Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med. 2011 May-Jun;9(3):257-67. doi: 10.1370/afm.1243. PMID: 21555754
- Wagner SC. Proton Pump Inhibitors and Bone Health: What the Orthopaedic Surgeon Needs to Know. JBJS Rev. 2018 Dec 18. doi: 10.2106/JBJS.RVW.18.00029. [Epub ahead of print] No abstract available. PMID: 30562209