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There is growing evidence that inflammation may be one of the causal factors of osteoporosis. Several cytokines such as IL-1, IL-6, RANKL, OPG, and M-CSF were implicated in the pathogenesis of osteoporosis. These cytokines are important determinants of osteoclast differentiation and its bone resorptive activity. Anticytokine therapy using cytokine antagonists such as IL-receptor antagonist and TNF-binding protein was able to suppress the activity of the respective cytokines and prevent bone loss. Several animal studies have shown that vitamin E in the forms of palm-derived tocotrienol and α-tocopherol may prevent osteoporosis in rat models by suppressing IL-1 and IL-6. Free radicals are known to activate transcription factor NFκB which leads to the production of bone resorbing cytokines. Vitamin E, a potent antioxidant, may be able to neutralise free radicals before they could activate NFκB, therefore suppressing cytokine production and osteoporosis. Vitamin E has also been shown to inhibit COX-2, the enzyme involved in inflammatory reactions. Of the two types of vitamin E studied, tocotrienol seemed to be better than tocopherol in terms of its ability to suppress bone-resorbing cytokines.

Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone-formation and increase in bone-resorption activity. Estrogen is able to suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and TNF-α. This is why these cytokines are elevated in postmenopausal women. Studies have shown that estrogen reduction is able to stimulate focal inflammation in bone. Labisia pumila (LP) which is known to exert phytoestrogenic effect can be used as an alternative to ERT which can produce positive effects on bone without causing side effects. LP contains antioxidant as well as exerting anti-inflammatory effect which can act as free radical scavenger, thus inhibiting TNF-α production and COX-2 expression which leads to decline in RANKL expression, resulting in reduction in osteoclast activity which consequently reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and antioxidative properties that make LP an effective agent against osteoporosis.