Evidence for Skeletal Resistance to Parathyroid Hormone in Magnesium Deficiency

Abstract

AB S T R A C T Hypocalcemia during magnesium (Mg) depletion has been well described, but the precise mechanism(s) responsible for its occurrence is not yet fully understood. The hypocalcemia has been ascribed to decreased parathyroid hormone (PTH) secretion as well as skeletal resistance to PTH. Whereas the former is well established, controversy exists as to whether or not Mg depletion results in skeletal resistance to PTH. These studies examine the skeletal response to PTH in normal dogs and dogs fed a Mg-free diet for 4-6 mo. Isolated tibia from normal (serum Mg 1.83±0.1 mg/100 ml) and experimental dogs (serum Mg 1.34+0.15 mg/100 ml) were perfused with Krebs-Henseleit buffer during a constant infusion of 3 ng/ml of synthetic bovine PTH 1-34 (syn b-PTH 1-34). The arteriovenous (A-V) difference for immunoreactive PTH (iPTH) across seven normal bones was 37.5+3%. In contrast, the A-V difference for iPTH was markedly depressed to 10.1±1% across seven bones from Mg-depleted dogs. These findings correlated well with a biological effect (cyclic AMP [cAMP] production) of syn b-PTH 1-34 on bone. In control bones, cAMP production rose from a basal level of 5.8±0.2 to 17.5±0.7 pmol/min after syn b-PTH 1-34 infusion. In experimental bones, basal cAMP production was significantly lower than in controls, 4.5±0.1 pmol/min, and increased to only 7.1±0.4 pmol/ min after syn b-PTH 1-34 infusion. Even when PTH concentrations were increased to 20 ng/ml, cAMP pro-

Effects of a deficient magnesium supply during the dry period on bone turnover of dairy cows at parturition

“…Research concerning the effects of a low Mg supply on calcium (Ca) mobilisation of cows has shown that hypomagnesaemic cows had lower Ca mobilisation rates in response to hypocalcaemia induced by the intravenous infusion of disodium ethylenediaminetetra-acetate (Na2EDTA) than normomagnesaemic cows (4,7,30). In studies with rats it was found that the rates of bone mineralisation (12,32), bone formation (12) and bone resorption (12) in Mg-deficient rats were lower than in rats which had been fed adequate Mg. Histological examination of bones from Mg-deficient dogs showed a picture compatible with skeletal inactivity (8). These observations indicate that in Mgdeficient animals the rate of bone turnover is decreased.…”

“…The lower plasma Pi levels in the low-Mg cows were associated with lower urinary P-to-creatinine ratios. Low plasma Pi concentrations also have been reported in Mg-deficient calves (25), growing rats (26) and adult dogs (8). Rude et al (29) reported low circulating levels of 1,25-dihydroxycholecalciferol (1,25-DHCC) in magnesium-deficient humans.…”

Clinical Consequences and Management of Hypomagnesemia

“…Acute hypomagnesaemia has the opposite effect; however, profound Mg 2ϩ depletion decreases the release of PTH and induces skeletal resistance to PTH and severe hypocalcemia. 2 Consequently, profound Mg 2ϩ deficiency causes tetany, cardiac arrhythmia, and bone instability and encourages renal stone formation. Mg 2ϩ deficiency has also been reported in 20 to 60% of patients in intensive care units (ICU).…”

Functional hypoparathyroidism secondary to magnesium deficiency in long-term users of proton pump inhibitor

“…Дефицит магния нарушает нормаль-ные секреторные механизмы и чувствительность тканей к ПТГ, влияя на функцию фосфоинозитольной системы и/или уменьшение активности аденилатциклазы в око-лощитовидных железах и органах-мишенях, поскольку оба процесса магний-зависимы. Также продемонстриро-вано, что для индукции резистентности органов-мише-ней требуется большая степень недостаточности магния, чем для изменения секреции ПТГ [27][28][29][30]. При резистент-ности костей и почек к ПТГ наблюдается развитие гипо-кальциемии в результате отсутствия стимуляции 1α-ги-дроксилирования витамина D в почках паратгормоном, что приводит к дефициту витамина D и снижению резор-бции костной ткани [20].…”