Published online Feb 28, 2023. doi: 10.3748/wjg.v29.i8.1374
Peer-review started: November 12, 2022
First decision: January 2, 2023
Revised: January 15, 2023
Accepted: February 15, 2023
Article in press: February 15, 2023
Published online: February 28, 2023
Chronic pancreatitis (CP) is a multifactorial fibro-inflammatory syndrome is characterized by nutritional deficiencies, systemic inflammation, and etiological factors like alcohol or smoking may disrupt the balance between bone formation and resorption. These maladaptive alterations may cause osteopenia and osteoporosis, resulting in fragility fractures which result from low energy trauma and have significant implications on quality of life.
Multiple large-sized studies on CP patients including those from multicenter cohorts have investigated the burden of bone disease in CP as well as their association with nutritional, anthropometric, and inflammatory parameters. Thus, with quantitative data on covariates and fragility fractures available, a synthesis of evidence is pertinent.
This systematic review and meta-analysis sought to quantify the prevalence of osteopenia, osteoporosis, and fragility fractures in CP patients and delineate clinical parameters which impact their occurrence.
The study included systematic review and then metanalysis of studies describing bone disease in CP patients. A preregistered systematic search enabled identification of original studies from Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until October 2022. The metanalysis was performed using random effect model and the outcomes of interest included prevalence of osteopenia, osteoporosis, and fragility fractures. To assess the association of these outcomes with covariates metaregression using random effect model was performed.
Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis. The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2% (95%CI: 35.2%-47.3%) and 20.9% (95%CI: 14.9%-27.6%), respectively. The pooled prevalence of fragility fractures described among CP was 5.9% (95%CI: 3.9%-8.4%). Meta-regression showed no associations of bone outcomes in CP patients with mean age, sex distribution, body mass index, alcohol or smoking exposure, diabetes, serum parathyroid levels, and vitamin D deficiency with prevalence of osteopenia, osteoporosis or fragility fractures. A significant association of pancreatic enzyme replacement therapy use with prevalence of osteoporosis [coefficient: 1.7 (95%CI: 0.6-2.8); P < 0.0001]. Due to sparse data on systemic inflammation, CP severity, and bone mineralization parameters a formal meta-analysis was not feasible.
This meta-analysis confirms significant bone disease: Osteopenia, osteoporosis, and fragility fractures in CP patients. Although pancreatic enzyme use had significant association with osteoporosis, the link between osteopathy and various patient or study-specific factors remains unclear. Further investigation is needed for delineation of at-risk population, to understand the mechanisms of CP-related bone disease, and assess the therapeutic response to treatment modalities.
Our study calls for dedicated studies targeting delineation of confounders and identification of at-risk features in CP patients. There is also a knowledge gap in therapeutic response among CP patients with bone disease.