ABSTRACT
Greater level of parathyroid hormone (PTH) than healthy subject is required to maintain appropriate bone turnover in dialysis patients. The skeletal resistance to PTH is the most important genesis of this phenomenon and the mechanism has been elucidated by the recent molecular biological techniques. Insufficient level of PTH induces not only adynamic bone disease but also cardiovascular diseases by ectopic calcification in soft tissues. Cardiovascular calcification is an important risk factor for the prognosis of dialysis patients, so the development of new therapeutic tools, that can adequately control PTH levels without hypercalcemia and hyperphosphatemia, are expected.
Subject(s)
Bone Diseases/etiology , Parathyroid Hormone/deficiency , Renal Dialysis/adverse effects , Cardiovascular Diseases/etiology , Humans , SyndromeABSTRACT
BACKGROUND: The impetus to develop percutaneous calcitriol injection therapy (PCIT) was the lack of therapeutic tools to treat secondary hyperparathyroidism (2HPT) resistant to medical therapy. METHODS: Nine dialysis patients resistant to intravenous calcitriol or calcitriol analogues underwent daily PCIT 5-10 times consecutively. The PCIT involved the injection of a volume of calcitriol equal to that of the enlarged parathyroid glands (PTGs) under ultrasonographic guidance. All patients had follow-up intravenous calcitriol after PCIT. RESULTS: The serum intact PTH concentration was markedly reduced following PCIT and was maintained for 12 weeks with intravenous calcitriol without significant changes in serum adjusted calcium and phosphorus concentrations. All patients tolerated PCIT without serious adverse events. Serum bone alkaline phosphatase concentrations and the volume of the enlarged PTGs were also significantly reduced. CONCLUSION: PCIT is a safe and effective treatment, which may also suppress parathyroid hyperplasia and improve bone turnover for refractory 2HPT.
Subject(s)
Calcitriol/administration & dosage , Calcium Channel Agonists/administration & dosage , Hyperparathyroidism, Secondary/drug therapy , Hyperparathyroidism, Secondary/etiology , Uremia/complications , Aged , Alkaline Phosphatase/metabolism , Biomarkers , Bone and Bones/enzymology , Bone and Bones/metabolism , Female , Humans , Hyperparathyroidism, Secondary/blood , Injections, Intralesional , Male , Middle Aged , Osmolar Concentration , Parathyroid Glands/diagnostic imaging , Parathyroid Hormone/blood , Time Factors , UltrasonographyABSTRACT
Classic pathogeneses of secondary hyperparathyroidism (2HPT), hyperphosphatemia, vitamin D deficiency, and hypocalcemia, have been treated by the administration of phosphorus binders and vitamin D derivatives. However, these therapies have not brought about a successful result. The main reason could be attributed to hypercalcemia resulting from the administration of calcium salts as a phosphorus binder and the calcemic action of vitamin D. To prevent hypercalcemia, non-calcium-containing phosphorus binders and vitamin D analogues, which suppress parathyroid hormone (PTH) secretion with minimum calcemic action, have been developed. Furthermore, calcimimetics that stimulate the calcium-sensing receptor of parathyroid cells and suppress PTH secretion are now under clinical trial. Direct injection therapy of vitamin D analogues or calcimimetics into the parathyroid gland also has been reported. These new strategies are expected to effectively and safely suppress 2HPT, which has been resistant to conventional medical treatments.
Subject(s)
Hyperparathyroidism/drug therapy , Animals , Epoxy Compounds/therapeutic use , Humans , Hyperparathyroidism/etiology , Phosphorus/metabolism , Polyamines , Polyethylenes/therapeutic use , Sevelamer , Vitamin D/analogs & derivatives , Vitamin D/therapeutic useABSTRACT
Hyperphosphatemia, vitamin D deficiency, and resulted hypocalcemia have been regarded as classical pathogeneses of secondary hyperparathyroidism. These factors have been treated by the administration of phosphorus binder and vitamin D derivatives. However, these therapies have not brought about a successful result for the prevention and treatment of secondary hyperparathyroidism. The reason could be mainly attributed to the hypercalcemia that results from the administration of calcium salts as a phosphorus binder and the calcemic action of vitamin D. To prevent hypercalcemia, non-calcium containing phosphorus binder (sevelamer hydrochloride) and vitamin D analogues, which suppress PTH secretion with minimum calcemic action, have been developed. These new vitamin D analogues include 19-nor-1-alpha, 25-dihydroxyvitamin D2 (paricalcitol), 1-alpha-hydroxyvitamin D2 (doxercalciferol), 22oxa-calcitriol (maxacalcitol) and F6-calcitriol (falecalcitriol). Furthermore, calcimimetics that stimulate calcium-sensing receptor of parathyroid cells as calcium and suppress PTH secretion are now under clinical trial. Percutaneous direct injection therapy of vitamin D, vitamin D analogue or calcimimetics into parathyroid gland has also been reported. The combination of these new strategies is expected to effectively and safely suppresses secondary hyperparathyroidism that has been resistant to conventional medical treatments.
