Generalized arterial calcification of infancy is an intractable ectopic mineralization disorder caused by mutations in the ENPP1 gene, resulting in reduced plasma inorganic pyrophosphate (PPi) levels. We previously characterized the Enpp1(asj) mutant mouse as a model of generalized arterial calcification of infancy, and we have now explored the potential efficacy of bisphosphonates, nonhydrolyz...

INTRODUCTION Long-term glucocorticoid therapy, a major risk factor for the development of osteoporosis, is often necessary in chronically ill patients. At present there are no generally accepted guidelines for the prevention or treatment of steroid-induced osteoporosis. METHODS In an open prospective study we investigated 99 patients with chronic rheumatic diseases receiving > or = 5 mg/day o...

Alendronate is a potent inhibitor of bone resorption. To investigate the relationship between antiresorptive activity and bone-related side effects, we studied the effect of 2 months of daily alendronate (0.04, 0.2, 1.0 or 5.0 mg/kg/day) treatment on the strength of the femoral shaft and neck and on the bone mass of ovariectomized rats. The p.o. administration regimen began immediately after ov...

T4 RNA ligase catalyzes the synthesis of ATP beta,gamma-bisphosphonate analogues, using the following substrates with the relative velocity rates indicated between brackets: methylenebisphosphonate (pCH(2)p) (100), clodronate (pCCl(2)p) (52), and etidronate (pC(OH)(CH(3))p) (4). The presence of pyrophosphatase about doubled the rate of these syntheses. Pamidronate (pC(OH)(CH(2)-CH(2)-NH(2))p), ...

Bisphosphonates are antiatherosclerotic, suppress monocyte-macrophages, and modulate proinflammatory mediators. Prostaglandin (PG) E(2), thromboxane (TX) A(2), and cyclooxygenase-2 (COX-2) enzyme are involved in inflammation and atherosclerosis. We studied the effects of four bisphosphonates (etidronate, clodronate, tiludronate, and alendronate) on PGE(2) and TXB(2) production in human whole bl...

The effect of therapeutic agents on trabecular bone loss in the mandible was investigated in ovariectomized rats. Eighty-seven Wistar SPF female rats were ovariectomized (OVX) or given a sham operation (Sham), and maintained on a diet containing 0.1% calcium. Four weeks later, groups of OVX rats were treated with estriol (E3), calcitonin (CT), etidronate, or 2-carboxyethylgermanium sesquioxide ...

This report describes a case of pulmonary alveolar microlithiasis that was diagnosed in an 8.5-year-old girl by high-resolution computed tomography (CT) and open lung biopsy. Presence of symptoms (productive cough, fever), their periodic occurrence (lasting up to 1 week), and comparatively long asymptomatic periods should be emphasized. Despite extensive X-ray abnormalities, tests of pulmonary ...