Jennifer Hofmann, DMSc, MS, PA-C, and Jean Covino, DHSc, MPA, PA-C

Gastroesophageal reflux disease (GERD) is a common gastrointestinal (GI) disorder characterized by the regurgitation of stomach contents into the esophagus causing troublesome symptoms and/or damage to the esophageal mucosa.

GERD affects approximately 20% of the US population, and it is one of the most common GI disorders seen by health care practitioners in the outpatient setting.

The clinical manifestations of GERD are variable. Classic symptoms include heartburn and regurgitation or the flow of gastric contents into the upper esophagus and pharynx. Other clinical manifestations of GERD include belching, dysphagia, epigastric pain, nausea, and odynophagia. Extraesophageal symptoms can occur in an atypical GERD presentation, and they include asthma, chest pain, cough, dysphonia, hoarseness, and laryngitis.

Treatment of GERD requires a combination of lifestyle modifications and pharmacologic therapy. Lifestyle modifications for GERD include avoiding alcohol, avoiding foods that worsen symptoms, avoiding meals 2 to 3 hours before bedtime, elevating the head of one’s bed by 6 inches, and smoking cessation. Weight loss in patients who are obese or overweight also improves GERD.

The frequency and severity of GERD symptoms, and/or the presence of Barrett’s esophagus or erosive esophagitis guide pharmacologic therapy. Patients with mild symptoms that occur infrequently, such as less than twice per week, can use low-dose H2 receptor antagonists (H2RAs): cimetidine 200 mg twice daily; famotidine 10 mg twice daily; or nizatidine 75 mg twice daily. H2 antagonists can be used as needed, and they begin working within 60 to 90 minutes and last several hours.

 H2 antagonists are generally well-tolerated, though cimetidine can cause gynecomastia and impotence with long-term use. Cimetidine is a potent inhibitor of the P450 system and can cause drug interactions. Antacids can be used as needed for symptoms which occur less than once a week. Antacids containing aluminum hydroxide, calcium carbonate, or magnesium trisilicate combinations work within 5 to 10 minutes and last for up to an hour. Aluminum containing antacids may cause aluminum retention in patients with significant renal impairment.

Patients who have 2 or more episodes per week of GERD or with severe GERD symptoms who fail to improve with H2RAs and/or patients with erosive esophagitis require proton pump inhibitors (PPIs) therapy. Proton pump inhibitors, such as dexlansoprazole, esomeprazole lansoprazole, omeprazole, pantoprazole, and rabeprazole, taken once daily at standard dosages are recommended for 8 weeks.

PPIs are most effective when taken 30 to 60 minutes prior to meals, usually before breakfast. Patients who develop recurrent GERD symptoms after an 8-week PPI course can be retreated with repeated 8-week courses and may require long-term maintenance therapy. Patients with early (<3 months of discontinuing acid suppression) and/or refractory recurrent symptoms may require referral for an upper endoscopy.7

PPIs are associated with adverse effects, particularly with long-term therapy. GI effects include increased risk for enteric infections, including C. difficile and multi-drug resistant Enterobacterales colonization. Long-term PPIs can cause malabsorption of minerals and vitamins, specifically hypomagnesemia, and vitamin B12 and PPIs may affect oral iron absorption. Long-term PPI therapy may slightly increase the risk for fractures of the hip, spine, and wrist. Patients with risk factors for osteoporosis who require PPIs should take calcium citrate and vitamin D supplements.

 PPIs can cause acute interstitial nephritis, and they may increase the risk for the development or progression of chronic kidney disease.

 PPIs may increase the risk for pneumonia, particularly in patients who are hospitalized.

Lifestyle modifications are recommended for all patients with GERD. Patients with infrequent, intermittent, or mild symptoms can use low-dose histamine 2 receptor antagonists, such as antacids or famotidine, as needed. Patients with erosive esophagitis, failure to respond to H2As, or frequent or severe symptoms require once-daily standard dose PPIs for 8 weeks.

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Articles

Treatment of gastroesophageal reflux disease requires a combination of lifestyle modifications and medications. 

What Is the Pharmacotherapy of GERD? 

Probiotics are live organisms that have a symbiotic relationship with the body, most often in the gastrointestinal (GI) tract.

The most common probiotics included in various formulations are bidifobacteria, lactobacilli, and the yeast 

 Probiotics are available in a wide range of products, formulations and strains. 

Evidence indicates that certain probiotics are possibly effective for GI conditions, such as antibiotic-associated diarrhea, chronic pouchitis associated with ulcerative colitis, constipation, diarrhea in adults and children, Helicobacter pylori in conjunction with standard therapies, irritable bowel syndrome (IBS), and reducing the risk of C. difficile infection.

The natural medicines database generally defines a “possibly effective” rating as “some clinical evidence supporting its use for a specific indication.”

However, the evidence is limited by quality, quantity, or contradictory findings.

Products rated “possibly effective” might be beneficial but do not have enough high-quality evidence to recommend for most individuals.

In 2020, the American Gastroenterological Association (AGA) published clinical practice guidelines on the role of probiotics for gastrointestinal diseases.

 The AGA concluded that certain probiotics may be beneficial for preventing C. difficile in patients taking antibiotics, but the quality of evidence was low and thus required further study. The AGA concluded similar findings for effectiveness of probiotics in patients with IBS and inflammatory bowel disease (IBD). An 8-strain combination probiotic including various lactobacillus and bifidobacteria species was helpful in patients with pouchitis related to IBD. Evidence also supported the use of certain bifidobacterial- and lactobacilli-containing probiotics in preterm infants to prevent necrotizing enterocolitis.

Probiotics are safe and well tolerated when taken appropriately in generally healthy people. There are some reports of mild GI effects, such as bloating, diarrhea, and flatulence.

 summarizes the most commonly used probiotics.

 Common Probiotic Products, Formulation/Strains, and Overview of Clinical Efficacy

Probiotics play a key role in the maintenance of immunologic equilibrium in the gastrointestinal tract through the direct interaction with immune cells. There is high-quality evidence that probiotics are effective for acute infectious diarrhea, antibiotic-associated diarrhea, Clostridium difficile–associated diarrhea, functional constipation, H pylori eradication, and IBS. Probiotics may improve human health, nutrition, and regulation of common GI abnormalities.

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https://naturalmedicines.therapeuticresearch.com/about-us/editorial-principles-and-process.aspx

2. Su GL, Ko CW, Bercik P, et al. AGA clinical practice guidelines on the role of probiotics in the management of gastrointestinal disorders. 

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3. Probiotics. What works and what doesn’t. Natural Medicines. March 20, 2020. Accessed August 1, 2022. https://naturalmedicines.therapeuticresearch.com/news/news-items/2020/march/probiotics-what-works-and-what-doesn%E2%80%99t.aspx

4. Comparison of common probiotic products. 

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5. Guyonnet D, Schlumberger A, Mhamdi L, Jakob S, Chassany O. Fermented milk containing bifidobacterium lactis DN-173 010 improves gastrointestinal well-being and digestive symptoms in women reporting minor digestive symptoms: a randomized, double-blind, parallel, controlled study. 

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6. Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. 

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7. Riezzo G, Orlando A, D'Attoma B, Linsalata A, Martulli M, Russo F. Randomized double-blind placebo-controlled trial on Lactobacillus reuteri DSM 17938: improvement in symptoms and bowel habit in functional constipation. 

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8. Poonyam P, Chotivitayatarakorn P, Vilaichone RK. High effective of 14-day high-dose PPI- bismuth-containing quadruple therapy with probiotics supplement for helicobacter pylori eradication: a double blinded-randomized placebo-controlled study. 

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9. Blaabjerg S, Artzi DM, Aabenhus R. Probiotics for the prevention of antibiotic-associated diarrhea in outpatients: a systematic review and meta-analysis. 

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10. Zhou BG, Chen LX, Li B, Wan LY, YW A. Saccharomyces boulardii as an adjuvant therapy for Helicobacter pylori eradication: a systematic review and meta-analysis with trial sequential analysis. 

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12. Wang Z, He Y, Zheng Y. Probiotics for the treatment of bacterial vaginosis: a meta-analysis. 

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13. Dimidi E, Christodoulides S, Fragkos KC, Scott SM, Whelan K. The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials. 

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14. Visbiome. Product inserts. Accessed August 1, 2022. https://www.visbiome.com/pages/product-inserts

15. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. 

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The live organisms help maintain immunologic equilibrium through direct interaction with immune cells.

Probiotics Play Key Role in the Gastrointestinal Tract

Osteoporosis is a systemic skeletal disease involving low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone fragility and fracture risk.

Bone density corresponds to the amount of mineral within a volume, and bone quality depends on architecture, bone matrix composition, bone turnover, damage accumulation, and mineralization.

 Osteoporosis develops silently over years before it becomes apparent through bone mineral density (BMD) screening or fractures. Fragility fractures are the main physical manifestation and occur at diverse sites, such as the distal radius, proximal femur, and vertebral bodies.

Recommend a dual-energy x-ray absorptiometry (DXA) to check BMD and screen for osteoporosis in the following patients at high risk

Adults on chronic glucocorticoid therapy, such as oral prednisone ≥5 mg/day for 3 or more months or an equivalent

Individuals aged 50 years and older with a recent low-trauma fracture

Other patients may also be good candidates for a DXA to check BMD, especially those with multiple risk factors. Assess risk factors to see if BMD testing is warranted with a thorough history in men aged 50 to 69 years or postmenopausal women younger than age 65 years with the following medical concerns

Excessive alcohol intake of 3 or more drinks per day

Radiographic osteopenia (DXA T-score between -1 and -2.5)

Taking medications that decrease BMD, such as aromatase inhibitors, glucocorticoids, GnRH agonists, phenobarbital, or phenytoin

There are 3 different categories of bone health for classification purposes:

: BMD 1 standard deviation or less below that of young white women reference mean (ie, T-score of −1 or greater)

: BMD between 1 and 2.5 standard deviations below that of young white women reference mean (ie, T-score between −1 and −2.5)

: BMD more than 2.5 standard deviations below that of young white women reference mean (ie, 

There are specific indications for pharmacotherapy:

T-score of −2.5 or less (ie, or worse) in distal third of radius, femoral neck, spine, or total hip

T-score from −1 down to −2.5 in distal third of radius, femoral neck, spine, or total hip, and fragility fracture of hip or spine

T-score from −1 down to −2.5 in distal third of radius, femoral neck, spine, or total hip, and FRAX score shows that that 10-year probability of hip fracture is 3% or greater or the 10-year probability of a major osteoporotic fracture is 20% or more

There are different approaches to screening. Some think that it is not necessary to check a DXA in patients who are receiving osteoporosis treatment because women receiving osteoporosis treatment may have reduced fractures, regardless of the impact on BMD. Others recommend continuing to check a DXA during treatment until BMD has stabilized or after 3 to 5 years of bisphosphonate therapy.

There are several pharmacotherapeutic options for osteoporosis treatment. Medications are classified mechanistically as antiresorptive agents that slow bone breakdown or anabolic “bone building” agents.

Antiresorptive medications include intravenous (IV) and oral bisphosphonates; selective estrogen receptor modulators (SERMs), specifically raloxifene and calcitonin nasal spray; and subcutaneous denosumab. Romosozumab-aqqg is a subcutaneously administered monoclonal antibody with anabolic/antiresorptive properties.

Anabolic agents are the subcutaneous parathyroid hormone analogs abaloparatide and teriparatide. Oral bisphosphonates, such as alendronate or risendronate, are generally preferred first-line agents for osteoporosis prevention and treatment in most patients. The choice of osteoporosis medication depends on multiple factors, including cost, osteoporosis fracture risk and severity, route of administration, and tolerability. The 

details the adverse effects (AEs), contraindications, and dosing of osteoporosis medications.

There are specific circumstances for which other osteoporosis medications may be considered.Raloxifene may be an option for women at high risk for breast cancer and in women who cannot tolerate bisphosphonates or denosumab.

 Calcitonin may be an option to reduce acute bone pain associated with vertebral fractures as well.

Patients with severe osteoporosis and very high fracture risk who cannot tolerate or respond poorly to IV and oral bisphosphonates may be candidates for anabolic agents abaloparatide or teriparatide or alternatively romosomuzab.

 Denosumab is an alternative to anabolic agents for high-risk older patients who cannot take or tolerate or respond poorly to bisphosphonates.

AE indicates adverse effect; BMD, bone mineral density; IV, intravenous; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein; and SERM, selective estrogen receptor modulator.

Osteoporosis is a common medical condition that increases fracture risk and requires individualized screening and management. Lifestyle management includes adequate vitamin D and calcium intake, increased physical activity, and smoking cessation. Oral bisphosphonates are first line for most patients with osteoporosis. Other agents may be reserved for high-risk patients who are intolerant or poorly responsive to bisphosphonates. Follow-up BMD testing is recommended to monitor response to therapy.

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 is a clinical associate professor at Pace University’s College of Health Professions in New York, New York.

 is a clinical professor at a department chairperson at Pace University’s College of Health Professions.

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Osteoporosis is a common medical condition that increases fracture risk and may require patients to make lifestyle changes.


Jennifer Hofmann, DMSc, MS, PA-C, and Jean Covino, DHSc, MPA, PA-C

Articles

What Is the Pharmacotherapy of GERD?

Probiotics Play Key Role in the Gastrointestinal Tract

Osteoporosis Requires Individualized Screening and Management