Exploring the Role of Cissus quadrangularis in Osteoporosis Management.

Cissus quadrangularis (CQ) is a Vitaceae-derived medicinal plant rich in flavonoids, phytosterols, triterpenoids, vitamins, and bone-relevant minerals, conferring combined antioxidant, anti-inflammatory, phytoestrogenic, and osteoanabolic properties that modulate key pathways involved in bone remodeling. This narrative review aims to synthesize preclinical and clinical evidence on CQ as a potential adjunct in osteoporosis management. Preclinical studies demonstrate that CQ enhances osteoblast differentiation, collagen and matrix deposition, and mineralization, while inhibiting osteoclastogenesis and inflammatory osteoclastogenic cytokines, leading to improved bone microarchitecture, bone mineral density, and callus formation in fracture and estrogen-deficiency models. CQ phytobioactives have also been successfully integrated into advanced biomaterials, exosome-like vesicles, and self‑emulsifying drug delivery systems, improving bioavailability, osseointegration, and regenerative performance in critical-sized defects and implant models. Clinical data, although limited and heterogeneous, consistently indicate that CQ accelerates fracture healing, reduces bone pain, and increases functional recovery in maxillofacial and mandibular fractures, with favorable effects on serum calcium, alkaline phosphatase, and osteopontin expression and without major safety concerns based on available short-term data. In postmenopausal osteopenia, randomized trials show that 24‑week oral CQ stabilizes bone turnover markers and delays bone loss, albeit without short‑term gains in bone mineral density. CQ thus emerges as a multi-target, generally well-tolerated candidate for integrative osteoporosis care, particularly for early bone loss (i.e., osteopenia), fracture healing, and osteoprotection during antiresorptive drug holidays (i.e., temporary suspension of bisphosphonate therapy, particularly in the context of dental procedures). However, the absence of standardized formulations, small sample sizes, short follow-ups, and lack of head‑to‑head comparisons with standard anti‑osteoporotic therapies currently available underscore the need for long-term, multicenter randomized controlled studies using bioavailable, well-characterized CQ preparations.