Early acid suppression therapy may predispose children to fractures
Exposure to acid suppression therapy (AST), such as proton pump inhibitors (PPIs), within the first year of life appears to pose an increased fracture risk in children, with the risk amplified by days of use and earlier initiation, a study has found.
The investigators, however, stressed that that the findings should not be interpreted to suggest that PPIs or histamine H2-receptor antagonists (H2RAs) alone explain fractures, which is important in suspected cases of nonaccidental trauma. Rather, results indicate that longer AST use and earlier initiation may increase fracture hazard.
“Practitioners should be aware of the potential for fracture when considering treatment with AST versus lifestyle changes and watchful waiting. If AST use is necessary, providers should limit prescriptions to a single drug and limit their duration when possible,” they added.
The current study included 851,631 children (median age, 5.8 years), among whom 97,286 (11 percent) were prescribed AST in the first year of life (PPI only, n=7,998; H2RA only, n=71,578; both drugs, n=17,710). Children with early AST exposure were more likely to be male, born preterm and with low birthweight. None of the children had osteogenesis imperfecta, cholestasis or experienced child maltreatment.
Children prescribed vs not prescribed AST within their first year of life had higher total fracture rates before (19 vs 16 per 1,000 person-years) and after 1 year of age (24 vs 21 per 1,000 person-years). Of note, first fracture occurred at an earlier age in those with early AST exposure (3.9 vs 4.5 years). [Pediatrics 2019;144:e20182625]
In multivariable Cox proportional hazard models, increased fracture risk was associated with use of PPI monotherapy (hazard ratio [HR], 1.23, 95 percent CI, 1.14–1.31) and both a PPI and an H2RA in the first year of life (HR, 1.31, 1.25–1.37).
Fracture hazard markedly increased with duration of AST use, suggesting a potential dose-dependent response, and with younger age of AST initiation with PPIs, alone or in combination with H2RAs. PPI use for 0–30 and >150 days carried a 19-percent and 41-percent increase in the risk, respectively, while PPI–H2RA exposure for 0–120, 120–192 and >338 days carried corresponding 17-percent, 31-percent and 50-percent risk increases.
Meanwhile, compared with no AST prescriptions <5 years of age, PPI initiation at 0–6 and 6–12 months of life was associated with a 23-percent and 21-percent increased fracture hazard, respectively. The corresponding risk increases associated with PPI–H2RA initiation at 0–6 and 6–12 months of life were 32 percent and 23 percent.
H2RA use alone did not significantly impact the risk of fractures.
The present data are in line with adult studies implicating AST in the risk of osteoporotic fracture, the investigators said. “Results are also consistent with research linking fracture with early PPI use in infants who [a]re sick and healthy, [as well as] with findings that PPIs d[o] not increase fracture risk in older children, because AST initiation after age 1 [i]s not associated with fracture.” [Rev Bras Ortop 2015;50:232-238; J Pediatr 2019:207:148-153; Osteoporos Int 2015;26:2501-2507]
In an accompanying editorial, Dr Mary Boruta from the Duke University Medical Center and her colleagues commented that prescribing patterns of acid suppression medication in children may necessitate changing considering investigations revealing a clear link between use of such drugs and adverse effects. “This is especially true in the setting of data showing limited clinical improvement with their use.” [Pediatrics 2019;144:e20190909]
“As discussed in recent societal practice guidelines, providers need to collaborate with their patients’ families to better understand the risks and benefits of such medications and consider offering nonmedication therapies that may be more beneficial,” Boruta and the others added. [J Pediatr Gastroenterol Nutr 2018;66:516-554]