Magnesium Deficiency and Bone Loss After Cardiac Transplantation

Abstract

Magnesium depletion adversely affects many phases of skeletal metabolism and has been implicated as a risk factor in several forms of osteoporosis. Magnesium deficiency has also been reported after cardiac transplantation. To evaluate whether altered magnesium homeostasis could be related to the pathogenesis of early bone loss after cardiac transplantation, we prospectively measured serum and urinary magnesium and evaluated them with respect to biochemical indices of mineral metabolism and rates of bone loss. The study population included 60 patients (45 men, 15 women) aged 53 ± 11 years (SD) with measurements of biochemistries and bone mineral density by dual-energy X-ray absorptiometry before and 3 months after transplantation. All received prednisone, cyclosporine A, and azathioprine, plus calcium (1000 mg) and vitamin D (400 IU). After transplantation, serum magnesium decreased by 16 ± 15% (SD) from 2.0 ± 0.3 mg/dl to 1.6 ± 0.2 mg/dl (normal 1.8-2.2 mg/dl; p < 0.0001), accompanied by an increase in the fractional excretion of magnesium (7.1 ± 3.9% to 13.3 ± 5.6%; p < 0.0017). Forty-three patients with low 3-month serum magnesium levels (р 1.7 mg/dl) sustained 41% less bone loss at the lumbar spine (4.0 ± 4.6% vs. 6.8 ± 5.3%; p = 0.051) and 58% less bone loss at the femoral neck (3.1 ± 5.9% vs. 7.3 ± 5.6%; p < 0.01), despite receiving similar doses of prednisone and cyclosporine A. Of the biochemical parameters measured (including renal function, serum calcium, phosphorus, vitamin D metabolites, osteocalcin, urinary calcium, and markers of bone resorption), only intact parathyroid hormone (PTH) levels, which were 40% lower in patients with low serum magnesium levels differed significantly (45 ± 23 pg/ml vs. 74 ± 60 pg/ml; p = 0.019). Patients with low serum magnesium levels also had evidence of lower bone turnover. In summary, a highly significant decline in serum magnesium concentrations, associated with continued urinary magnesium losses, occurs after cardiac transplantation. Patients with low serum magnesium levels had significantly lower rates of bone loss, lower serum PTH concentrations, and lower bone turnover. Although the precise mechanisms by which the reduction in serum magnesium tends to protect against bone loss in the early post-transplantation period remain to be elucidated, reduced serum PTH and lower rates of bone turnover are likely to be important factors. (J Bone Miner Res 1999;14:295-303)

Ibandronate Prevents Bone Loss and Reduces Vertebral Fracture Risk in Male Cardiac Transplant Patients: A Randomized Double-Blind, Placebo-Controlled Trial

“…Another prospective study showed a protective effect on bone loss of low serum magnesium levels, as are commonly encountered in transplant patients, likely because of lower PTH and lower bone turnover, but with no obvious effects on fracture rates. (46) In a previous study in liver transplant patients, we found a similar negative association of magnesium and BMD (29) ; however, in this analysis, serum magnesium levels did not change during the study period.…”

Bone mineral content and mineral metabolism during cyclosporine treatment of nephrotic syndrome

“…1,34,35 In the present study, reduced GFR 36 and histologic abnormalities on sequential renal biopsies 37 were absent, and except for the relatively higher urinary ␤ 2 -globulin concentrations in patients receiving Cy, there were no other indications of tubulointerstitial dysfunction. 38,39 Lower doses and trough levels of Cy employed in our patients may account for these findings.…”

“…Paracellin downregulation by Cy 40 resulting in urinary Mg wasting and hypomagnesemia may contribute to decreased bone formation, osteopenia, and bone fragility. 14,35 Our patients on Cy-Rx displayed lower serum Mg concentrations (range 1.6-2.0 mg/ dL) but not as low as following Tx, 14 and increased urinary FEMg 35 was absent. Cyclosporine, by down-regulating calbindin-D28k, 41 also causes hypercalciuria, hypocalcemia,and intratubular calcification, but these were not present in our study.…”

Associations of Calcium and Magnesium in Serum and Hair with Bone Mineral Density in Premenopausal Women

“…Other studies have reported that serum calcium or magnesium were positively associated with BMD in peri-or postmenopausal women, [5,6,8,11,14] but contradictory results showing a negative association between serum magnesium and BMD were also reported in people with Crohn's disease [15] or cardiac transplantation. [16] In another studies, serum ionized and total magnesium levels were inversely related to serum level of estrogen in postmenopausal women, [20] and total plasma calcium and magnesium levels increased at menopause, which was thought to be a result of increased bone loss, but these increased levels were reversed by treatment with ethinyl estradiol. [21] Although the diversity of study participants and the variety of included confounders can partially account for these differences, interactions of various nutrients or hormones are also likely to be associated with them.…”

“…[7][8][9] Previous studies have shown that dietary intake and blood or intracellular levels of calcium and magnesium are significantly associated with bone density. [4,[10][11][12][13][14][15][16][17] Although many studies have reported a positive association of calcium and magnesium with bone mineral density (BMD), results are not consistent [15][16][17] and are difficult to compare owing to the diversity of study participants and failure to adjust for major confounders.…”