The renin-angiotensin system (RAS) is an endocrine system that governs body fluid and electrolyte balance, blood pressure, and it is also involved in bone metabolism. Components of the RAS are expressed in human bone cell and can activate a local RAS response that leads to increased bone turnover and decreased bone density.
Several reports have been published on the effects of angiotensin II (Ang II) on bone cell function in vitro, including the inhibition of osteoblastic differentiation and mineralization, the stimulation of proliferation and collagen synthesis in osteoblasts, and the stimulation of osteoclastic bone resorption. The majority of the studies on the effects of ACE inhibitors or Ang II type 1 receptor blockers on bone, including those in humans and animal models, suggests that pharmacological inhibition of the RAS pathway can lead to decreased fracture risk and increased bone mass.
Some authors found that renin activity (PRA) was directly associated with bone mineral density (BMD) in highly selected samples of patients. Association of PRA with BMD seems to be specific for trabecular bone, and it has also been suggested in an animal model of osteoporosis. In addition, there is evidence that there are shared genetic pathways underlying these associations.
Primary aldosteronism (PA), characterized by aldosterone excess, and renin and Ang II suppression, has probably another mechanism of action to impair bone health. In an animal model, as well as in humans, aldosterone excess was associated with an increased urinary and fecal loss of Ca++, Mg++, in turn inducing hypocalcemia, hypomagnesemia and secondary hyperparathyroidism, that was rescued by adrenalectomy or treatment with mineralocorticoid receptor antagonist (MRA). These alterations seem to lead to low bone mass and fragility fractures whereas surgery or MRA therapy improved bone mass. Moreover, the possible relation between PA and bone was suggested by data coming from genome wide association between indexes of bone strength and some genes involved in aldosterone pathways. In this regard it should be mentioned that the expression of mineralocorticoid receptor on bone cells could actually suggest a still unknown direct effect of mineralocorticoids on the skeletal tissue.