There is an intricate balance between systemic acid-base homeostasis and skeletal integrity and the pathophysiological mechanisms by which metabolic acidosis influences bone metabolism can be complex.
Metabolic acidosis initiates a series of adaptive responses aimed at correcting the acid-base imbalance. One critical adaptation involves the skeletal system acting as a buffer. To neutralize excess hydrogen ions, bone releases alkaline salts such as calcium carbonate and calcium phosphate into the extracellular fluid. While this buffering action aids in mitigating acidosis, it comes at the expense of bone mineral content and structural strength.
Chronic metabolic acidosis has been shown to enhance osteoclastic bone resorption and suppress osteoblastic bone formation. The acidotic environment increases the expression of receptor activator of nuclear factor κB ligand (RANKL) and decreases osteoprotegerin (OPG) levels, promoting osteoclast differentiation and activity. Concurrently, acidosis impairs osteoblast function by inhibiting collagen synthesis and reducing alkaline phosphatase activity, which are essential for bone matrix formation and mineralization.
At the molecular level, acidosis alters the expression of genes and proteins involved in bone remodeling. It influences the production of cytokines and growth factors such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and insulin-like growth factor-1 (IGF-1), which modulate osteoclast and osteoblast activity. Additionally, acidosis can affect the hormonal regulation of bone metabolism, including alterations in parathyroid hormone (PTH) secretion and vitamin D metabolism, further exacerbating bone demineralization.
Clinically, chronic metabolic acidosis is particularly relevant in patients with renal insufficiency, where the kidneys' ability to excrete acid is compromised. Persistent acidosis in these patients can lead to osteopenia, osteoporosis, and an increased risk of fractures. Moreover, the bone disease associated with acidosis can contribute to the morbidity seen in chronic kidney disease (CKD) patients.
Understanding these mechanisms underscores the importance of early detection and management of metabolic acidosis to preserve bone health. Complementary therapeutic interventions may include:
Metabolic acidosis:
Bushinsky, David A, and Nancy S Krieger. “Effects of acid on bone.” Kidney international vol. 101,6 (2022): 1160-1170. doi:10.1016/j.kint.2022.02.032
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