Decreased potassium stimulates bone resorption

Metabolic acidosis induces net calcium efflux (J(Ca)(+)) from cultured bone, in part, through an increase in osteoclastic resorption and a decrease in osteoblastic formation. In humans provision of base as potassium (K+) citrate, but not sodium (Na+) citrate, reduces urine Ca (U-Ca), and oral KHCO3 decreases bone resorption and Uc, in postmenopausal women. Potassium deprivation alone leads to an increase in U-Ca. To determine whether decreased extracellular K+ concentration ([K+]) at a constant pH, P-CO2, and [HCO2-] alters J(Ca)(+) and bone cell activity, we measured J(Ca)(+), osteoblastic collagen synthesis, and osteoclastic beta-glucuronidase release from neonatal mouse calvariae cultured for 48 h in medium of varying [K+]. Calvariae were cultured in control medium (approximate to 4 mM [K+]) or medium with mildly low K+ (MLK, approximate to 3 mM: [K+]), very low K+ (VLK, approximate to 2 mM [K+]), or extremely low K+ (ELK, approximate to 1 mM [K+]) (n greater than or equal to 9 in each group). Compared with control, ELK, but not MLK or VLK, resulted in a marked increase in J(Ca)(+) and an increase in beta-glucuronidase release and a decrease in collagen synthesis. J(Ca)(+), was correlated directly with medium beta-glucuronidase activity and inversely with collagen synthesis. To determine whether the reduction in medium [K+] was associated with a decrease in intracellular pH (pH(i)), we measured pH(i) in MC3T3-E1 cells, a mouse osteoblastic cell line. Incubation in 1 mM [K+] led to a significant decrease in pH(i) compared with 3 mM [K+]. Thus incubation in a reduced [K+] medium stimulates J(Ca)(+) and osteoclastic enzyme release and inhibits osteoblastic collagen synthesis, which may be mediated by a reduction in bone cell pH.