Abstract-Vascular calcification is a common problem among the elderly and those with chronic kidney disease (CKD) and diabetes. The process of tunica media vascular calcification in CKD appears to involve a phenotypic change in the vascular smooth muscle cell (VSMC) resulting in cell-mediated mineralization of the extracellular matrix. The bone morphogenetic proteins (BMPs) are important regulators in orthotopic bone formation, and their localization at sites of vascular calcification raises the question of their role. In this review, we will discuss the actions of the BMPs in vascular calcification. Although the role of BMP-2 in vascular calcification is not proven, it has been the most studied member of the BMP family in this disease process. The role of BMP-2 may be through inducing osteoblastic differentiation of VSMCs through induction of MSX-2, or by inducing apoptosis of VSMCs, a process thought critical in the initiation of vascular calcification. Additionally, BMP-2 may be related to loss of regulation of the matrix Gla protein. A second BMP, BMP-7, less studied than BMP-2 may have opposing actions in vascular calcification. In postnatal life, BMP-7 is expressed primarily in the kidney, and expression is diminished by renal injury. BMP-7 is an important regulator of skeletal remodeling and the VSMC phenotype. BMP-7 restores skeletal anabolic balance in animal models of CKD with disordered skeletal modeling, also reducing serum phosphate in the process. BMP-7 also reverses vascular calcification in CKD, and reduction in vascular calcification is due, in part, to reduced serum phosphate, an important inducer of VSMC-mediated vascular mineralization and in part to direct actions on the VSMC. 15,17 or myofibroblasts into the vessel wall accounts for the mineralizing cell population in the medial artery calcification of diabetes. Although the search for the origin of the mineralizing cell goes on, it is also imperative to understand the stimulus that drives it. One possible stimulus is the bone morphogenetic proteins (BMPs), which along with the Wnt family of glycoproteins 18 and sex steroids, are the known important anabolic factors in bone formation and determinants of bone mineral content. 19 -24 Because they are essential to normal bone formation, it is intuitive to consider that the BMPs may also be important in the pathophysiology of vascular calcification. Although definitive evidence to support this is lacking, there is considerable supportive evidence, and we will discuss the basic physiology of the BMPs, concentrating primarily on BMP-2 and -7, in this review. We will discuss how BMP-2 expression in the vasculature may entrain a transcriptional program that leads to an osteoblastlike cellular phenotype and matrix mineralization. Furthermore, we will discuss preliminary studies of the protective actions of another BMP, BMP-7, on vascular calcification. The Bone Morphogenetic ProteinsThe BMPs are a group of at least 30 proteins named for their osteoinductive properties that have important develop...

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Background: Vitamin D deficiency is common in CKD and dialysis patients. Studies suggest a physiologic autocrine and/or paracrine role for 1,25(OH)D produced via 1α-hydroxylase in tissues such as vascular smooth muscle, breast, prostate, and bone marrow. Studies have not yet defined the optimal dose and duration of vitamin D necessary to replete and maintain stores in dialysis patients, or whether it is safe or beneficial. Methods: We performed a review of the prevalence of vitamin D deficiency and the safety and effectiveness of ergocalciferol oral supplementation (vitamin D₂, 50,000 IU monthly) given to hemodialysis patients during dialysis May to October 2005 in St. Louis (latitude 38°). Results: Among the 119-patient cohort present for the entire 6 months, 25(OH)D was (mean ± SD) 16.9 ± 8.5 ng/ml, (91% < 30 ng/ml) and increased to 53.6 ± 16.3 ng/ml (p < 0.001), (95% > 30 ng/ml, and none > 100 ng/ml). Initial versus 6 mo. serum calcium (9.1 ± 0.56 vs. 9.2 ± 0.70), phosphorus (5.25 ± 1.38 vs. 5.11 ± 1.31), Ca × P, and paricalcitol dose (10.3 ± 9.6 vs. 11.3 ± 9.2 mcg/week) were not significantly different. No hypercalcemia could be attributed to supplementation. Mean hemoglobin did not change significantly (11.96 ± 1.4 vs. 11.69 ± 1.4, p = 0.124), but most patients experienced a reduced weekly epoetin dose. Epoetin dose decreased in 64% of patients, and increased in 28%. Conclusions: We conclude that the vast majority of hemodialysis patients are vitamin D-deficient; monthly ergocalciferol 50,000 IU is safe and effective in normalizing serum 25(OH)D levels and may have an epoetin-sparing effect.