Abstract
BACKGROUND: Maintaining bone health is vital, particularly for aging populations prone to bone disorders. Cissus quadrangularis (CQ), a traditional medicinal plant, is increasingly recognized for its potential benefits in promoting bone health, including the effects on bone-related biomarkers promoting bone healing and bone density improvement. This study aimed to evaluate the effects of CQ on bone-related biomarkers in humans as the primary objective and to assess its impact on other clinical outcomes as a secondary objective. METHODS: A systematic search of PubMed, Embase, Scopus, and the Cochrane Library databases was conducted up to April 2025. This systematic review included studies with participants receiving Cissus quadrangularis, those reporting bone biomarkers, and those with a randomized controlled design involving human participants. No restrictions were placed on age, sex, disease severity, or administration route. The quality of the studies included was assessed using the revised Cochrane risk-of-bias tool (RoB-2), while the overall strength of evidence was appraised using the GRADE approach. The summary effect measure was the standardized mean difference (SMD) with 95% confidence intervals (95% CI). RESULTS: Seven studies, comprising a total of 354 participants, met the inclusion criteria for meta-analysis. The analysis revealed that CQ intervention significantly elevated serum parathyroid hormone levels (SMD = 1.23; 95% CI = 0.79 to 1.67; p < 0.0001). However, the CQ intervention did not result in significant changes in other bone-related biomarkers, including calcium, phosphorus, and serum alkaline phosphatase. The RoB-2 revealed that most studies had some concerns about bias, with two evaluated as having a high risk. The certainty of evidence was very low for all four parameters assessed by GRADE. CONCLUSION: The CQ intervention was significantly associated with increased serum parathyroid hormone levels, with no significant effects on other bone-related biomarkers. Although there were a limited number of studies, these findings suggest its potential for modulating bone health; however, further research is needed to confirm these results and explore its clinical applications. TRIAL REGISTRATION: The study protocol was prospectively registered with PROSPERO, and the registration number is CRD42023435351. CLINICAL TRIAL NUMBER: Not applicable.