(18)F-sodium fluoride PET/CT for the in vivo visualization of Mönckeberg's sclerosis in a diabetic patient.

Diabetes is a major frequent cause of atherosclerosis vascular disease. Arterial calcification in diabetic patients is responsible for peripheral vascular involvement. Molecular imaging using (18)F-sodium fluoride ((18)F-NaF) positron emission tomography (PET)/computed tomography (CT) has been recently proposed as a marker to study the in vivo mineralization process in the atheroma plaque. A 69-year-old man with a history of type 2 diabetes and no clinical evidence of peripheral arterial disease underwent an (18)F-NaF PET/CT scan. A linear, well-defined (18)F-NaF uptake was detected along the femoral arteries. In addition, the CT component of the PET/CT identified an unsuspected "tram-track" calcification in his femoral arteries, suggestive of medial calcification (Mönckeberg's sclerosis). In other vascular territories, focal (18)F-NaF uptake was also detected in carotid and aorta atheroma plaques. Molecular imaging with (18)F-NaF PET/CT might provide new functional information about the in vivo vascular calcification process in diabetic patients.

The clinical significance of medial arterial calcification in end-stage renal disease in women.

Medial arterial calcification is common in advanced kidney disease but its impact on cardiovascular disease is uncertain because imaging techniques used to date cannot reliably distinguish it from atherosclerotic calcification. We have previously shown that breast arterial calcification (BAC) is exclusively medial and is a marker of generalized medial calcification in end-stage renal disease (ESRD). Therefore, the presence of BAC on mammograms in 202 women with ESRD (mean duration 4.1 years) was correlated with cardiovascular events to determine the clinical significance of medial arterial calcification. BAC was found in 58% of the study participants and was significantly associated with age, diabetes, and ESRD duration. Both coronary artery (27 vs. 15%) and peripheral arterial disease (PAD; 19 vs. 4%) were more likely in patients with BAC but only the latter persisted after accounting for other factors (odds ratio 4.6; 95% confidence interval 1.2-15). In 142 women without clinical events before mammography, BAC was associated with a greater incidence of new PAD events (13 vs. 3%) but not coronary artery disease events (11 vs. 11%). Thus, BAC is strongly and independently associated with PAD in women with ESRD and may be predictive of clinical events. This suggests that medial arterial calcification is a clinically significant lesion that may contribute to the accelerated PAD in ESRD.

Clinical decision-making for vitamin K-1 and K-2 deficiency and coronary artery calcification with warfarin therapy: are diet, factor Xa inhibitors or both the answer?

Coronary artery calcification is a recognised risk factor for ischaemic heart disease and mortality. Evidence is now strong that Mönckeberg's arteriosclerosis, a form of vascular calcification, can be attributable to vitamin K deficiency, but that vitamin K-2, especially the MK-4 form from foods like cheese can be protective. Warfarin blocks the recycling of hepatic and peripheral vitamin K leading to secondary vitamin K deficiency with adverse effects on vasculature, bone, kidneys, brain and other tissues and systems (inflammatory, immune function and neoplasia at least). There is individual susceptibility to vitamin K deficiency and warfarin sensitivity, partly explicable in terms of genetic polymorphisms, epigenetics, diet and pharmacotherapy. The emergence of extensive coronary calcification in a man with atrial fibrillation treated for a decade with warfarin is described by way of illustration and to raise the present clinical management conundrums. Finally, a putative set of recommendations is provided.

A case of ochronosis with gout and Monckeberg arteries.

Alkaptonuria is an inborn error of amino acid metabolism. A defect in tyrosine metabolism that results in accumulation of homogentisic acid in connective tissue, especially cartilage, has long been known. Degenerative arthropathy, especially of the knee and spine, develops at a relatively early age in adults. Accumulation also occurs in heart valves, and there may be a predisposition to atherosclerosis. We describe a 72-year-old man with ochronosis, gouty arthritis of both hands, and monckeberg arteries.

[Variance of expressions of extracellular matrix components and effects of anti-osteoporotic drugs on Mönckeberg's arteriosclerosis].

Mönckeberg-type arteriosclerosis occurs as a complication in diabetic, uremic patients and in postmenoposal women. It has been shown that arterial calcification generates loss of elasticity in tunica media. We have already reported that the expression of tropoelastin (TE), the precursor protein of elastin, is suppressed by arterial calcification, although no changes of mRNA expression of the other elastic fiber components, such as fibrillins, was observed. We examined the effects of bisphosphonates, known as anti-osteoporotic drugs, in inorganic phosphate (Pi)-induced calcified bovine aortic smooth muscle cells (BASMCs) (in vitro arterial calcification model). Treatment with the bisphosphonate risedronate, significantly inhibited calcium deposition in the arterial calcification model. Risedronate also inhibited suppression of TE mRNA expression and the progression of osteopontin (OPN) and core binding factor-alpha1 (Cbfa1), an osteogenic transcription factor, by BASMCs calcification. Basically, bisphosphonates could inhibit phenotypic transition such as SMC to osteoblast-like cell. Inhibitory effects of bisphosphonates were also shown in female Sprague-Dawley rats with calcinosis induced by administration of an over-dose of vitamin D2 (in vivo arterial calcification model). It is known that arterial calcification is accelerated by oxidative low-density lipoprotein (oxLDL). Therefore we examined the effects of 7-ketocholesterol (7kc), a component of oxLDL, on in vitro arterial calcification. Thereupon, it was revealed that 7kc drastically accelerated Pi-induced calcification, and risedronate completely restored the calcification and mRNA expression accelerated by 7kc.

Monckeberg's calciphylaxis with necrosis of the glans penis: a case presentation.

Monckeberg's calcific sclerosis of the media of the small-sized and medium-sized arteries is a well described and potentially life-threatening condition seen almost exclusively in patients with end-stage renal disease (ESRD) and with hyperparathyroidism. Penile gangrene resulting from this entity is associated with a mortality as high as 64%. A 65-year-old man with ESRD on dialysis for 6 years was referred to Harborview Medical Center with severe penile pain and partial necrosis of his glans penis, which progressed despite medical management. The patient had previously undergone amputations on all four extremities. After intraoperative biopsies of the proximal corpora cavernosa and spongiosum demonstrated viable tissue, he underwent partial penectomy. Pathologic evaluation revealed calciphylaxis within the media of the penile vessels. Two months later the patient had persistent wound-healing issues with intractable pain and thus underwent a complete penectomy with ultimate resolution of his severe pain.

[Vascular calcification in advanced secondary hyperparathyroidism].

Cardiovascular disease is one of the largest cause of mortality in maintenance hemodialysis patients. Vascular calcifications frequently encountered in hemodialysis patients. In advanced uremic secondary hyperparathyroidism model mice, vascular calcifications were observed in their aorta, by Kossa staining. This mouse model may be a useful model to study vascular calcification in maintenance hemodialysis patients.