Delayed bone healing, non-union, and prolonged rehabilitation following fractures or orthopedic surgeries are persistent challenges in global healthcare, affecting patients and clinical practices across regions. Low-Level Laser Therapy (LLLT), also referred to as photobiomodulation, has emerged as a non-invasive therapeutic approach increasingly explored in orthopedics. In vitro and in vivo studies have indicated its potential to modulate biological processes relevant to bone repair, though the underlying mechanisms and optimal application parameters remain areas of ongoing investigation. This article synthesizes key findings from a systematic review published in the International Journal of Molecular Sciences (DOI: 10.3390/ijms24087094) to provide a neutral, evidence-based overview of LLLT’s biological effects, clinical relevance, and current research status in bone healing.

Biological Mechanisms of LLLT in Bone Healing

LLLT involves the application of low-intensity light at specific wavelengths, distinct from high-intensity lasers used for ablative or cutting purposes, and operates without inducing thermal damage to tissues. The systematic review by Berni et al. (2023) summarizes the molecular pathways implicated in LLLT-mediated bone healing, based on aggregated data from preclinical studies:
Angiogenic Regulation: LLLT has been shown to upregulate the expression of pro-angiogenic growth factors, including Vascular Endothelial Growth Factor (VEGF), Fibroblast Growth Factors (FGF), and Platelet-Derived Growth Factor (PDGF). These factors facilitate the formation of new blood vessels, a critical process for delivering oxygen, nutrients, and signaling molecules to sites of bone repair.
Osteogenic Differentiation: The therapy modulates key intracellular signaling pathways, such as PI3K/AKT and MAPK/ERK, which regulate the differentiation of stem cells into osteoblasts—cells responsible for bone matrix synthesis and mineralization. This differentiation is further supported by the upregulation of osteogenic transcription factors, including runt-related transcription factor 2 (Runx2).
Gene Expression Modulation: LLLT influences the expression of bone-specific genes, including collagen type 1 (Col1), osteocalcin (Ocn), osteopontin (Opn), bone sialoprotein (Ibsp), and bone morphogenetic proteins (BMPs). These genes play essential roles in extracellular matrix formation, bone mineralization, and the overall progression of fracture healing.
Notably, the review highlights that LLLT’s biological effects are highly dependent on technical parameters, including wavelength, energy density, irradiation duration, and frequency. Variations in these parameters, as well as differences in cell types or tissue microenvironments, may contribute to variability in observed outcomes across studies.

Potential Clinical Applications in Orthopedics

While preclinical data supports LLLT’s biological activity, its clinical utility in orthopedics is centered on several target scenarios, as outlined in the systematic review:
Fracture Healing: LLLT has been investigated as an adjunctive therapy for acute fractures and non-unions, with preclinical studies suggesting accelerated bone union. However, clinical translation of these findings remains limited, and further human trials are required to confirm efficacy in diverse fracture types.
Post-Surgical Rehabilitation: Following orthopedic procedures such as joint replacement, spinal fusion, or osteotomy, LLLT has been explored for its potential to reduce inflammation, support soft tissue healing, and minimize complications associated with implant integration. Its non-invasive nature makes it a candidate for complementary use alongside conventional post-operative care.
Bone Regeneration in Pathological Conditions: For patients with bone loss due to trauma, degenerative diseases, or comorbidities (e.g., osteoporosis), LLLT has been studied for its ability to enhance endogenous regenerative capacity. However, evidence for efficacy in these complex clinical scenarios is currently preliminary.
The review emphasizes that LLLT’s clinical application is predicated on personalized parameter adjustment, as standardized protocols have not yet been validated across patient populations or clinical contexts.

Conclusion

Low-Level Laser Therapy (LLLT) represents a promising area of research in bone healing, with preclinical data supporting its modulation of angiogenic, osteogenic, and gene regulatory pathways. However, clinical translation remains constrained by limited high-quality human evidence, variable parameter standardization, and incomplete mechanistic understanding. For global adoption, LLLT requires further large-scale clinical trials, regulatory alignment, and standardized training protocols. As research continues to address current gaps, LLLT may evolve into a complementary therapy in orthopedics, though its role in routine clinical practice will depend on rigorous validation across diverse patient populations and healthcare contexts.

References: Berni, M., Brancato, A.M., Torriani, C., Bina, V., Annunziata, S., Cornella, E., Trucchi, M., Jannelli, E., Mosconi, M., Gastaldi, G., Caliogna, L., Grassi, F.A., & Pasta, G. (2023). The Role of Low-Level Laser Therapy in Bone Healing: Systematic Review. International Journal of Molecular Sciences, 24(8), 7094. https://doi.org/10.3390/ijms24087094