The Experts below are selected from a list of 90 Experts worldwide ranked by ideXlab platform
Hirotoshi Morii - One of the best experts on this subject based on the ideXlab platform.
-
Falecalcitriol as a new therapeutic agent for secondary hyperparathyroidism
Clinical calcium, 2005Co-Authors: Hirotoshi MoriiAbstract:The 26 and 27 positions of vitamin D molecular structure of calcitriol were fluorinated with 3 atoms of fluorine each and the new compound was named Falecalcitriol (F6). This new compound was found to be 10 to 100 times more active compared with calcitriol depending on the target organs. As a mechanism of strong action of F6 it was discovered that F6 is hydroxylated at 23 position which has almost the same activity as the mother compound. It was also demonstrated that the PTH suppressive effect was relatively stronger than the calcium absorption action from the intestine. Thus F6 was authorized to be applied to the treatment of secondary hyperparathyoroidism in hemodialysed patients as well as to the treatment of hypoparathyroidism.
-
Management of calcium and bone abnormalities in hemodialysis patients.
Seminars in nephrology, 2004Co-Authors: Hirotoshi Morii, Tayuki Inoue, T. Takaaki Nishijima, T. Takashi Tomokuni, Takatoshi Ishikawa, T. Kenji Moriya, Nobuaki Kawai, T. Hiroyuki Araki, T. Misa Horio, Tsutomu ShigeokaAbstract:In chronic renal failure, hyperphosphatemia, hypocalcemia, hyperparathyroidism, reduced activation of vitamin D, decreased level of calcium-sensing receptor, osteitis fibrosa, and osteomalacia are features related to calcium abnormalities. Hyperparathyroidism is a risk factor for survival of hemodialysis patients as well as hypoparathyroidism, which is another feature in hemodialysis patients. Treatment of these abnormalities includes control of parathyroid hormone (PTH) secretion, counteracting hyperphosphatemia, correction of hypocalcemia, and others. Various kinds of vitamin D analogs have been introduced recently in addition to calcitriol and alfacalcidol, which have a rather long history (eg, maxacalcitol and Falecalcitriol). Sevelamer is a newly developed phosphate binder to treat soft-tissue calcification.
-
Efficacy and safety of oral Falecalcitriol in reducing parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism
Journal of Bone and Mineral Metabolism, 1998Co-Authors: Hirotoshi Morii, Yosuke Ogura, Shozo Koshikawa, Nobuhide Mimura, Masashi Suzuki, Kiyoshi Kurokawa, Fumiaki Marumo, Yoshindo Kawaguchi, Kenji Maeda, Yoshiki NishizawaAbstract:Based on research conducted so far, active vitamin D_3 is known to suppress the secretion of parathyroid hormone (PTH), which is stimulated by chronic renal failure. We investigated the effect and safety of Falecalcitriol, a new type of active vitamin D_3, in patients with secondary hyperparathyroidism accompanied by chronic renal failure in a multicenter study. In a double-blind study, 121 patients were randomly assigned to a Falecalcitriol group (63 patients) or a placebo group (58 patients). They received daily oral Falecalcitriol or placebo for 8 weeks. The change rates of intact PTH (i-PTH) , midregion PTH (m-PTH), and carboxy-terminal PTH (c-PTH) were determined as major evaluation parameters. The Falecalcitriol group showed a significant suppression ( P < .01) of 34.8% in i-PTH; in contrast, the placebo group recorded a significant rise ( P < .01) of 12.4%, with a significant difference ( P < .01) between the groups. The results for m-PTH and c-PTH were similar to those for i-PTH. Serum calcium, meanwhile, rose significantly ( P < .01) in the Falecalcitriol group after 2 weeks. The mean values, however, remained within the normal range, and the change rate was within 10%. Apart from the rise in serum calcium, there were no differences in adverse reactions from the placebo group. The results suggest that Falecalcitriol is an effective drug against secondary hyperparathyroidism with chronic renal failure because it significantly inhibits a rise in i-PTH under conditions that cause no large changes in serum calcium.
-
Efficacy and safety of long-term oral Falecalcitriol treatment in patients with renal osteodystrophy
Journal of Bone and Mineral Metabolism, 1998Co-Authors: Hirotoshi Morii, Tetsuro Inoue, Masao Fukunaga, Atsushi Shioi, Research Committee St-630Abstract:We investigated, in a multicenter study, the efficacy and safety of long-term administration of Falecalcitriol, a new active vitamin D_3, in patients with renal osteodystrophy of the osteitis fibrosa type associated with secondary hyperparathyroidism caused by chronic renal failure. Falecalcitriol was orally administered every day for 48 weeks. Administration was started at a dosage of 0.3 μg/day, and the dosage was changed whenever necessary according to serum calcium (Ca) level. As a result, significant inhibition of the bone resorption markers, i.e., intact parathyroid hormone (i-PTH), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr), was observed from the 8th week, and the bone formation markers, i.e., total activity and bone fraction of alkaline phosphatase, were also significantly inhibited from the 12th week. The bone mineral density (BMD) change rate in the bones of the whole body determined by dual-energy X-ray absorptiometry remained almost constant. When subjects were stratified according to the inhibition rate of bone metabolic parameters, BMD tended to increase in the group with strong inhibition and to decrease in the group with weak inhibition. Mean serum Ca level significantly increased from 9.5 mg/dl, but mean level was subsequently maintained at about 10 mg/dl until the end of administration by adjustment of the doses. These findings suggested that Falecalcitriol may inhibit and normalize accelerated bone metabolic turnover without inducing excessive increases in serum Ca level in secondary hyperparathyroidism. With respect to safety, no specific adverse reactions associated with the prolonged administration period were observed.
-
clinical efficacy and optimal dose of st 630 Falecalcitriol in secondary hyperparathyroidism in patients undergoing hemodialysis late phase ii multicenter trial
Nihon Toseki Igakkai Zasshi, 1997Co-Authors: Hirotoshi Morii, Yosuke Ogura, Shozo Koshikawa, Nobuhide Mimura, Masashi Suzuki, Kiyoshi Kurokawa, Yoshindo Kawaguchi, Yoshiki Nishizawa, Seishi Inoue, Yoshio SuzukiAbstract:慢性腎不全に伴う二次性副甲状腺機能亢進症に対する新規の活性型ビタミンD3製剤Falecalcitriol (ST-630) の有効性・安全性および至適投与量を二重盲検法による群間比較にて検討した. 最終全般改善度の判定は開始時に対するHS-PTHの変化率を指標に行ったところ, 各群の改善率 (「改善」以上の判定) は0.05μg/日群で31%, 0.15μg/日群で38%, 0.3μg/目群で59%であった. HS-PTHは0.05μg/日群で約20%の有意な上昇, 0.15μg/日群では上昇傾向がみられたが, 0.3μg/日群では約10%減少し, 0.05μg/日群と0.3μg/日群の間に有意差がみられた. このようにFalecalcitriolは用量依存的にHS-PTHの上昇抑制ないし低下作用を示した. C-PTHについてもHS-PTHと同様の変化がみられ, 0.3μg/日群での低下はC-PTHの方が明確であった.概括安全度については, 非安全率 (「ほぼ安全」以下と判定された症例) が0.05μg/日群2%, 0.15μg/日群9%, 0.3μg/日群20%であった. 0.3μg/日群の主な副作用としては高カルシウム血症が3例に, また徐脈・胸部違和感が1例に発現した. 高カルシウム血症発現例における血清カルシウム (アルブミン補正値) は最高で12.3mg/dlであったが, いずれも発現から20日以内に回復し, 特に問題とはならなかった. 血清カルシウムの平均値は0.3μg/日群でも投与期間を通じて正常範囲内を推移し, 血清リンの上昇も認められなかった. 重篤と考えられる副作用は0.15μg/日群の1例で肝機能障害が認められたが投与中止により軽快した.以上のようにFalecalcitriolは0.3μg/日投与により慢性腎不全に伴う二次性副甲状腺機能尤進症に対し優れた有効性を示し, 有効性・安全性の両面を考慮すると至適投与量は0.3μg/日であると考えられた.ただし, 高カルシウム血症には十分な注意が必要であり, 適切な間隔で血清カルシウムを検査することが安全性を確保する上で重要と考えられた.今後は, 今回把握された至適投与量を用いて対照薬を置いた客観的な比較試験, 長期投与時の有効性,安全性の検討, さらには骨病変に対する効果の検討などが必要と考えられた.
Alex J. Brown - One of the best experts on this subject based on the ideXlab platform.
-
Vitamin D analogs for secondary hyperparathyroidism: what does the future hold?
The Journal of steroid biochemistry and molecular biology, 2006Co-Authors: Alex J. BrownAbstract:Secondary hyperparathyroidism (2 degrees HPT) commonly develops in patients with chronic kidney disease (CKD) in response to high phosphate, low calcium and low 1,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)]. High PTH levels increase the rate of bone turnover, with a net efflux of calcium and phosphate leading to vascular calcification and coronary artery disease. Treatment of 2 degrees HPT with 1alpha,25(OH)(2)D(3) and calcium-based phosphate binders often produces hypercalcemia and over-suppression of PTH, resulting in adynamic bone that cannot buffer excess calcium and phosphate, which increases the risk of vascular calcification. It is essential, then, to reduce PTH levels to a range that supports normal bone turnover and minimizes ectopic calcification. Vitamin D analogs that inhibit PTH gene transcription and parathyroid hyperplasia, and that have less calcemic activity than 1alpha,25(OH)(2)D(3,) have provided a greater safety margin for the treatment of 2 degrees HPT, as well as enhancing the survival of CKD patients. Although several analogs with less calcemic activity are now used in patients (paricalcitol and doxercalciferol in the USA, and OCT and Falecalcitriol in Japan), efforts to develop even more selective analogs continue. Parathyroid glands express both 25-hydroxylase and 1alpha-hydroxylase and may be capable of activating prohormones or prodrugs to suppress PTH and parathyroid growth by an autocrine mechanism. Moreover, the introduction of non-calcium-based phosphate binders (sevelamer and lanthanum carbonate) and cinacalcet (an allosteric activator of the calcium receptor that reduces PTH and the serum calciumxphosphate product) may reduce the risk of hypercalcemia with vitamin D therapy. Combining these agents with higher doses of vitamin D compounds may achieve greater suppression of PTH and possibly enhance survival in patients with chronic kidney disease.
-
Vitamin D analogs for secondary hyperparathyroidism: what does the future hold?
The Journal of Steroid Biochemistry and Molecular Biology, 2006Co-Authors: Alex J. BrownAbstract:Secondary hyperparathyroidism (2°HPT) commonly develops in patients with chronic kidney disease (CKD) in response to high phosphate, low calcium and low 1,25-dihydroxyvitamin D 3 [1α,25(OH) 2 D 3 ]. High PTH levels increase the rate of bone turnover, with a net efflux of calcium and phosphate leading to vascular calcification and coronary artery disease. Treatment of 2°HPT with 1α,25(OH) 2 D 3 and calcium-based phosphate binders often produces hypercalcemia and over-suppression of PTH, resulting in adynamic bone that cannot buffer excess calcium and phosphate, which increases the risk of vascular calcification. It is essential, then, to reduce PTH levels to a range that supports normal bone turnover and minimizes ectopic calcification. Vitamin D analogs that inhibit PTH gene transcription and parathyroid hyperplasia, and that have less calcemic activity than 1 α,25(OH) 2 D 3, have provided a greater safety margin for the treatment of 2°HPT, as well as enhancing the survival of CKD patients. Although several analogs with less calcemic activity are now used in patients (paricalcitol and doxercalciferol in the USA, and OCT and Falecalcitriol in Japan), efforts to develop even more selective analogs continue. Parathyroid glands express both 25-hydroxylase and 1α-hydroxylase and may be capable of activating prohormones or prodrugs to suppress PTH and parathyroid growth by an autocrine mechanism. Moreover, the introduction of non-calcium-based phosphate binders (sevelamer and lanthanum carbonate) and cinacalcet (an allosteric activator of the calcium receptor that reduces PTH and the serum calcium x phosphate product) may reduce the risk of hypercalcemia with vitamin D therapy. Combining these agents with higher doses of vitamin D compounds may achieve greater suppression of PTH and possibly enhance survival in patients with chronic kidney disease. ©2007 Published by Elsevier Ltd.
-
Vitamin D Analogs
Treatments in Endocrinology, 2002Co-Authors: Alex J. Brown, Daniel W. CoyneAbstract:Patients with chronic renal failure frequently develop secondary hyperparathyroidism, primarily as a result of phosphate retention and low serum 1,25(OH)_2D_3. Replacement therapy with calcitriol or its synthetic precursor alfacalcidol [1α(OH)D_3] often produces hypercalcemia, especially when combined with calcium-based phosphate binders. In addition, the natural vitamin D compounds can exacerbate the hyperphosphatemia in patients with chronic renal failure. This combined increase in calcium and phosphate has been correlated with vascular calcification leading to coronary artery disease, the most common cause of mortality in renal patients. Several vitamin D analogs have now been developed that retain the direct suppressive action of calcitriol on the parathyroid glands but have less calcemic activity, thereby offering a safer and more effective means of controlling secondary hyperparathyroidism. Maxacalcitol [22-oxa-1,25(OH)_2D_3] and Falecalcitriol [1,25(OH)_2-26,27-F_6-D_3] are currently available in Japan, and paricalcitol [19-nor-1,25(OH)_2D_2] and doxercalciferol [1α(OH)D_2] are available in the US. The mechanisms by which these analogs exert their selective actions on the parathyroid glands are under investigation. The low calcemic activity of maxacalcitol has been attributed to its rapid clearance from the circulation. This prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of parathyroid hormone gene expression. The selectivity of the other analogs is achieved by distinct mechanisms. Understanding how these compounds exert their selective actions on the parathyroid glands will aid in the design of safer, more effective analogs.
-
Vitamin D analogues for secondary hyperparathyroidism
Nephrology Dialysis Transplantation, 2002Co-Authors: Alex J. Brown, Adriana Dusso, Eduardo SlatopolskyAbstract:Secondary hyperparathyroidism (2HPT), a common disorder in patients with chronic renal failure, develops in response to phosphate retention and low serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitriol). Replacement therapy with calcitriol or its precursor 1a-hydroxyvitamin D3 (1aOHD3, alfacalcidol) often produces hypercalcaemia, especially when combined with calcium-based phosphate binders. In addition, these vitamin D compounds can aggravate the hyperphosphataemia in these patients. Several vitamin D analogues have been developed that retain the direct suppressive action of 1,25(OH)2D3 on the parathyroid glands but have less calcaemic activity, thereby offering a safer and more effective means of controlling 2HPT. 1,25-Dihydroxy-19-norvitamin D2 (19-norD2) and 1a-hydroxyvitamin D2 (1aOHD2) are available in the US and 1,25-dihydroxy-22-oxavitamin D3 (22-oxacalcitriol, OCT) and 1,25-dihydroxy-26,26,26, 27,27,27-hexafluorovitamin D3 (1,25(OH)226,27F6 D3, Falecalcitriol) have been approved for use in Japan. Animal studies have demonstrated that OCT and 19-norD2 have a wider therapeutic window for suppression of parathyroid hormone (PTH) because of their lower calcaemic and phosphataemic activities. The low calcaemic activity of OCT has been attributed to its rapid clearance, which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression and parathyroid cell growth. The calcaemic activity of 19-norD2 diminishes with the duration of treatment by as yet unknown mechanisms. The lower toxicity of 1aOHD2, compared with 1aOHD3, has also been noted with chronic, but not acute administration, perhaps due to differential metabolism. The unique actions of Falecalcitriol may also result from an altered metabolism. A clear understanding of the molecular basis for the selectivity of vitamin D analogues on parathyroid function may allow the design of even more effective analogues.
-
Renal failure and vitamin D
Clinical calcium, 2002Co-Authors: Alex J. Brown, Adriana Dusso, Eduardo SlatopolskyAbstract:Secondary hyperparathyroidism (2HPT), a common disorder in patients with chronic renal failure, develops in response to phosphate retention and low serum 1,25-dihydroxyvitamin D(3) [1,25 (OH) (2)D(3), calcitriol] . Replacement therapy with calcitriol or its precursor 1alpha-hydroxyvitamin D(3) [1alpha (OH) D(3), alfacalcidol] often produces hypercalcemia and hyperphosphatemia in these patients. Several vitamin D analogues have been developed that retain the direct suppressive action of 1,25 (OH) (2)D(3) on the parathyroid glands but have less calcemic activity, therapy offering a safer and more effective means of controlling 2HPT. 1,25-D dihydroxy-19-norvitamin D(2) (19-nor D(2)) and 1alpha-hydroxyvitamin D(2) (1alphaOHD(2)) are available in the United States and 1,25-dihydrox-22-oxavitamin D(3) (22-oxacalcitriol, OCT) and 1,25-dihydroxy-26,26,26,27,27,27-hexafluorovitamin D(3) [1,25 (OH)(2)26,27F(6)D(3), Falecalcitriol] have been approved for use in Japan. Animal studies have demonstrated that OCT and 19-nor D(2) have a wider therapeutic window for suppression of parathyroid hormone (PTH) because of their lower calcemic activities of OCT has been attributed to its rapid clearance which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression and parathyroid cell growth. The calcemic activity of 19-norD(2) diminishes with the duration of treatment by as yet unknown mechanisms. The lower toxicity of 1alphaOHD(2), compared 1alphaOHD(3). has also been noted with chronic, but not acute administration, perhaps due to differential metabolism. The unique actions of Falecalcitriol may also result from altered metabolism. A clear understanding of the molecular basis for the selectivity of vitamin D analogues on parathyroid function may allow the design of even more effective analogues.
Eriko Kinugasa - One of the best experts on this subject based on the ideXlab platform.
-
Research on kidney and mineral metabolism in Japan: past, present, and future
Clinical and Experimental Nephrology, 2017Co-Authors: Masahide Mizobuchi, Hiroaki Ogata, Fumihiko Koiwa, Eriko Kinugasa, Tadao AkizawaAbstract:Since the identification of the kidney was the main site for the synthesis of calcitriol (1α, 25-dihydroxycholecalciferol), research on chronic kidney disease (CKD)-associated mineral metabolism disorders and their management has made rapid progress. Various active analogues of calcitriol have clinically become available for treating secondary hyperparathyroidism (SHPT), which is a representative mineral metabolism abnormality in CKD patients. A calcimimetic compound cinacalcet hydrochloride has also been developed for the medical management of SHPT through a different mechanism involving the calcium-sensing receptor. The concept of CKD-mineral and bone disorder (CKD-MBD) was proposed in 2006 to provide a comprehensive understanding of a disorder related to mineral metabolism abnormalities of CKD, based on the fact that these abnormalities are closely associated with cardiovascular disease as well as bone disorders (renal osteodystrophy). There has been a recent surge in the development of phosphate binders for CKD-MBD, focused on an effort to improve mortality. In Japan, high-quality basic and clinical research on CKD-MBD has led to the development of novel therapeutic drugs, such as maxacalcitol, Falecalcitriol, and bixalomer. New practice guidelines have been published and are widely adapted in clinical practice.
-
Comparison of oral Falecalcitriol and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism: a randomized, crossover trial.
Clinical nephrology, 2009Co-Authors: Hidetoshi Ito, Hiroaki Ogata, M Yamamoto, K Takahashi, Kanji Shishido, J Takahashi, Susumu Taguchi, Eriko KinugasaAbstract:Background Falecalcitriol is a novel vitamin D analog, which has a greater potential to suppress parathyroid hormone (PTH) and a longer half-life. There are few studies to compare clinical effects of oral Falecalcitriol treatment with those of intravenous calcitriol treatment. Methods Twenty-one patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with the two vitamin D analogs (12 weeks for each treatment). The primary endpoint measure was a decrease in serum intact PTH (iPTH) level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Results Both treatments decreased iPTH and whole PTH (wPTH) levels by similar degrees (iPTH, -200.1 +/- 107.0 with Falecalcitriol vs. -200.8 +/- 114.9 pg/ml with calcitriol, p = 0.9895; wPTH, -137.1 +/- 73.1 with Falecalcitriol vs. -120.4 +/- 81.1 pg/ml with calcitriol, p = 0.5603). Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. Although intravenous calcitriol treatment significantly changed intact osteocalcin and cross-linked N-telopeptide of type I collagen after 12 weeks, oral Falecalcitriol treatment did not change any bone metabolic marker level. Conclusion The present study showed that oral Falecalcitriol treatment is effective for PTH suppression, and Ca and P metabolism in hemodialysis patients with moderate to severe SHPT, as well as intravenous calcitriol administration.
-
Management of secondary hyperparathyroidism of dialysis patients.
Nephrology, 2003Co-Authors: Tadao Akizawa, Masahide Mizobuchi, Hiroaki Ogata, Motohiro Kamimura, Kazuhiro Shiizaki, Shinji Sumikado, Toshibumi Sakaguchi, Shigeo Negi, Eriko KinugasaAbstract:SUMMARY: 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.
Tadao Akizawa - One of the best experts on this subject based on the ideXlab platform.
-
Research on kidney and mineral metabolism in Japan: past, present, and future
Clinical and Experimental Nephrology, 2017Co-Authors: Masahide Mizobuchi, Hiroaki Ogata, Fumihiko Koiwa, Eriko Kinugasa, Tadao AkizawaAbstract:Since the identification of the kidney was the main site for the synthesis of calcitriol (1α, 25-dihydroxycholecalciferol), research on chronic kidney disease (CKD)-associated mineral metabolism disorders and their management has made rapid progress. Various active analogues of calcitriol have clinically become available for treating secondary hyperparathyroidism (SHPT), which is a representative mineral metabolism abnormality in CKD patients. A calcimimetic compound cinacalcet hydrochloride has also been developed for the medical management of SHPT through a different mechanism involving the calcium-sensing receptor. The concept of CKD-mineral and bone disorder (CKD-MBD) was proposed in 2006 to provide a comprehensive understanding of a disorder related to mineral metabolism abnormalities of CKD, based on the fact that these abnormalities are closely associated with cardiovascular disease as well as bone disorders (renal osteodystrophy). There has been a recent surge in the development of phosphate binders for CKD-MBD, focused on an effort to improve mortality. In Japan, high-quality basic and clinical research on CKD-MBD has led to the development of novel therapeutic drugs, such as maxacalcitol, Falecalcitriol, and bixalomer. New practice guidelines have been published and are widely adapted in clinical practice.
-
Management of secondary hyperparathyroidism of dialysis patients.
Nephrology, 2003Co-Authors: Tadao Akizawa, Masahide Mizobuchi, Hiroaki Ogata, Motohiro Kamimura, Kazuhiro Shiizaki, Shinji Sumikado, Toshibumi Sakaguchi, Shigeo Negi, Eriko KinugasaAbstract:SUMMARY: 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.
Research Committee St-630 - One of the best experts on this subject based on the ideXlab platform.
-
Efficacy and safety of long-term oral Falecalcitriol treatment in patients with renal osteodystrophy
Journal of Bone and Mineral Metabolism, 1998Co-Authors: Hirotoshi Morii, Tetsuro Inoue, Masao Fukunaga, Atsushi Shioi, Research Committee St-630Abstract:We investigated, in a multicenter study, the efficacy and safety of long-term administration of Falecalcitriol, a new active vitamin D_3, in patients with renal osteodystrophy of the osteitis fibrosa type associated with secondary hyperparathyroidism caused by chronic renal failure. Falecalcitriol was orally administered every day for 48 weeks. Administration was started at a dosage of 0.3 μg/day, and the dosage was changed whenever necessary according to serum calcium (Ca) level. As a result, significant inhibition of the bone resorption markers, i.e., intact parathyroid hormone (i-PTH), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr), was observed from the 8th week, and the bone formation markers, i.e., total activity and bone fraction of alkaline phosphatase, were also significantly inhibited from the 12th week. The bone mineral density (BMD) change rate in the bones of the whole body determined by dual-energy X-ray absorptiometry remained almost constant. When subjects were stratified according to the inhibition rate of bone metabolic parameters, BMD tended to increase in the group with strong inhibition and to decrease in the group with weak inhibition. Mean serum Ca level significantly increased from 9.5 mg/dl, but mean level was subsequently maintained at about 10 mg/dl until the end of administration by adjustment of the doses. These findings suggested that Falecalcitriol may inhibit and normalize accelerated bone metabolic turnover without inducing excessive increases in serum Ca level in secondary hyperparathyroidism. With respect to safety, no specific adverse reactions associated with the prolonged administration period were observed.