Review for 10.1186/s12876-025-03720-6 (2025)

Title: Prevalent Osteoporosis and Fracture Risk in Patients with Hepatic Cirrhosis: A Systematic
Review and Meta-analysis
Version: 0 Date: 16 Jan 2025
Reviewer's report:
Dear Editor,
Thank you for the opportunity to review the manuscript entitled "Incident Osteoporosis and
Fracture Risk in Patients with Hepatic Cirrhosis: A Systematic Review and Meta-analysis." The
authors present a thorough meta-analysis investigating the heightened risk of osteoporosis and
fractures in patients with hepatic cirrhosis, a topic of increasing clinical significance. The study
finds that cirrhotic patients are significantly more likely to experience osteoporosis and fractures
compared to healthy controls, providing important insights into the bone health complications
associated with cirrhosis.
Statistical Comments:
Heterogeneity in Bone Mineral Density (BMD) Analyses: While the manuscript appropriately
addresses heterogeneity through sensitivity analysis, the BMD results for the lumbar spine and
femoral neck still show considerable variability (I² > 50%). It would be helpful to explore
potential sources of this heterogeneity further, particularly in terms of the underlying etiology
of cirrhosis (e.g., viral, alcoholic, metabolic), as these factors may influence BMD outcomes.
Meta-Regression Findings: The meta-regression analysis suggests that male prevalence may
impact the association between cirrhosis and bone outcomes. However, the study could benefit
from exploring other potential confounders (e.g., age, comorbidities, medication use) in more
detail to assess their effects on the association between cirrhosis and osteoporosis risk.
Publication Bias and Sensitivity Analysis: The authors report no significant publication bias,
which is reassuring. However, further clarification on how the exclusion of certain studies, such
as Figueiredo et al., influenced the results could strengthen the interpretation of the findings.
Specifically, does the exclusion of these studies alter the generalizability of the conclusions for
certain patient subgroups?
Clinical Comments:
Clinical Implications of Fracture Risk: The finding that cirrhotic patients have a 2.3 times higher
risk of fractures compared to healthy controls is clinically significant. However, the manuscript
could further emphasize how these findings should influence clinical practice, particularly in the
context of screening and managing fracture risk in cirrhotic patients. What specific preventive
measures should be implemented in clinical settings for these patients?
Vitamin D and Calcium Deficiency: The manuscript appropriately discusses the role of vitamin
D and calcium deficiency in increasing fracture risk in cirrhosis patients. It would be beneficial
to explore how the current evidence could shape clinical guidelines for supplementation and
bone health monitoring in cirrhotic patients, particularly for those with advanced liver disease.
Integration into Fracture Risk Models: The authors suggest that cirrhosis should be integrated
into fracture risk models. It would be helpful if they could provide more concrete
recommendations on how cirrhosis could be incorporated into existing models like FRAX, or
whether new models might be needed to more accurately predict fracture risk in this population.