The role of immune system in various bone pathologies, such as osteoporosis, osteoarthritis, and rheumatoid arthritis is now well established. This had led to the emergence of a modern field of systems biology called as osteoimmunology, an integrated research between fields of immunology and bone biology under one umbrella. Osteoporosis is one of the most common inflammatory bone loss condition with more than 200 million individuals affected worldwide. T helper (Th) cells along with various other immune cells are major players involved in bone homeostasis. In the present review, we specifically discuss the role of various defined T lymphocyte subsets (Th cells comprising Th1, Th2, Th9, Th17, Th22, regulatory T cells, follicular helper T cells, natural killer T cells, γδ T cells, and CD8⁺ T cells) in the pathophysiology of osteoporosis. The study of the specific role of immune system in osteoporosis has now been proposed by our group as “immunoporosis: the immunology of osteoporosis” with special emphasis on the role of various subsets of T lymphocytes. The establishment of this new field had been need of the hour due to the emergence of novel roles of various T cell lymphocytes in accelerated bone loss observed during osteoporosis. Activated T cells either directly or indirectly through the secretion of various cytokines and factors modulate bone health and thereby regulate bone remodeling. Several studies have summarized the role of inflammation in pathogenesis of osteoporosis but very few reports had delineated the precise role of various T cell subsets in the pathobiology of osteoporosis. The present review thus for the first time clearly highlights and summarizes the role of various T lymphocytes in the development and pathophysiology of osteoporosis, giving birth to a new field of biology termed as “immunoporosis”. This novel field will thus provide an overview of the nexus between the cellular components of both bone and immune systems, responsible for the observed bone loss in osteoporosis. A molecular insight into the upcoming and novel field of immunoporosis would thus leads to development of innovative approaches for the prevention and treatment of osteoporosis.

Osteoporosis is one of the most important but often neglected bone disease associated with aging and postmenopausal condition leading to bone loss and fragility. Probiotics have been associated with various immunomodulatory properties and have the potential to ameliorate several inflammatory conditions including osteoporosis. Lactobacillus acidophilus (LA) was selected as probiotic of choice in our present study due its common availability and established immunomodulatory properties. In the present study, we report for the first time that administration of LA in ovariectomized (ovx) mice enhances both trabecular and cortical bone microarchitecture along with increasing the mineral density and heterogeneity of bones. This effect of LA administration is due to its immunomodulatory effect on host immune system. LA thus skews the Treg-Th17 cell balance by inhibiting osteoclastogenic Th17 cells and promoting anti-osteoclastogenic Treg cells in ovx mice. LA administration also suppressed expression of osteoclastogenic factors (IL-6, IL-17, TNF-α and RANKL) and increased expression of anti-osteoclastogenic factors (IL-10, IFN-γ). Taken together the present study for the first time clearly demonstrates the therapeutic potential of LA as an osteo-protective agent in enhancing bone health (via tweaking Treg-Th17 cell balance) in postmenopausal osteoporosis.

Osteoporosis is a systemic-skeletal disorder characterized by enhanced fragility of bones leading to increased rates of fractures and morbidity in large number of populations. Probiotics are known to be involved in management of various-inflammatory diseases including osteoporosis. But no study till date had delineated the immunomodulatory potential of Lactobacillus rhamnosus (LR) in bone-health. In the present study, we examined the effect of probiotic-LR on bone-health in ovariectomy (Ovx) induced postmenopausal mice model. In the present study, we for the first time report that LR inhibits osteoclastogenesis and modulates differentiation of Treg-Th17 cells under in vitro conditions. We further observed that LR attenuates bone loss under in vivo conditions in Ovx mice. Both the cortical and trabecular bone-content of Ovx+LR treated group was significantly higher than Ovx-group. Remarkably, the percentage of osteoclastogenic CD4⁺Rorγt⁺Th17 cells at distinct immunological sites such as BM, spleen, LN and PP were significantly reduced, whereas the percentage of anti-osteoclastogenic CD4⁺Foxp3⁺Tregs and CD8⁺Foxp3⁺Tregs were significantly enhanced in LR-treated group thereby resulting in inhibition of bone loss. The osteoprotective role of LR was further supported by serum cytokine data with a significant reduction in osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with enhancement in anti-osteoclastogenic cytokines (IL-4, IL-10, IFN-γ) in LR treated-group. Altogether, the present study for the first time establishes the osteoprotective role of LR on bone health, thus highlighting the immunomodulatory potential of LR in the treatment and management of various bone related diseases including osteoporosis.

The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application.