A New Look at the Most Successful Prodrugs for Active Vitamin D (D Hormone): Alfacalcidol and Doxercalciferol

Objective: Chronic hypoparathyroidism and its treatment may lead to symptoms and complications affecting quality of life. We determined complications in chronic hypoparathyroid patients. Design: Retrospective cross-sectional study of patients with chronic hypoparathyroidism treated with active vitamin D supplements in a tertiary care centre during the year 2015. Primary outcome parameters were history of kidney stones and seizures and presence of renal and cerebral calcifications on imaging. Secondary outcome parameters were current symptoms of paraesthesia/cramps, hospitalization due to hyper/hypocalcaemia and hypercalciuria. Subjects: One hundred and seventy patients were included -143 (84%) with post-surgical hypoparathyroidism (PSHP), 16 (9%) with non-surgical hypoparathyroidism (NSHP) and 11 (7%) with pseudo-hypoparathyroidism (PHP). Results: History of kidney stones and seizures was present in 15 and 9% of patients, respectively. Renal and cerebral imaging was performed in 51 and 26% of the patients, with 22 and 25% of these patients having renal and cerebral calcifications respectively. Both history of seizures and cerebral calcifications were significantly more in NSHP and PHP than in PSHP patients. No association was observed between seizures and cerebral calcifications. Cramps/paraesthesia were present in 16%, and hospitalization related to hypocalcaemia was reported in 5% of the patients. Calciuria was screened in 47% at the time of consultation, and in 76% of the patients during the past 5 years. In 36% of these patients, calciuria was increased. Conclusions: Patients with chronic hypoparathyroidism frequently develop ectopic calcifications. Non-surgical patients suffer more from seizures and cerebral calcifications than patients that developed hypoparathyroidism post surgery. There is a need for increased screening of long-term complications, according to the guidelines.

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“…The majority of the patients took alfacalcidol (21,22,23). The median dose of active vitamin D analogues did not differ between the three groups.…”

Section: Discussionmentioning

confidence: 90%

Long-term complications in patients with chronic hypoparathyroidism: a cross-sectional study

David

Moyson

Vanderschueren

et al. 2019

European Journal of Endocrinology

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“…Reduced synthesis of calcitriol in the kidneys, hypocalcemia, and hyperphosphatemia commonly occur in development of secondary hyperparathyroidism . Active forms of vitamin D are used to treat secondary hyperparathyroidism in dialysis patients through binding with greater or lesser selectivity to vitamin D receptors distributed throughout the entire body .…”

mentioning

confidence: 99%

Comparison of Paricalcitol and Calcitriol in Dialysis Patients With Secondary Hyperparathyroidism: A Meta‐Analysis of Randomized Controlled Studies

Zhang

Ju²,

Chen³

et al. 2018

Ther Apher Dial

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Paricalcitol and calcitriol are widely used for the treatment of secondary hyperparathyroidism in dialysis patients. We conducted a systematic review and meta-analysis to compare the efficacy and safety of paricalcitol and calcitriol for secondary hyperparathyroidism in dialysis patients. PubMed, EMbase, Web of Science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCT) assessing the efficacy of paricalcitol and calcitriol for secondary hyperparathyroidism in dialysis patients are included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Meta-analysis was carried out using the random-effect model. Six randomized controlled trials are included in the meta-analysis. Overall, compared with calcitriol treatment for secondary hyperparathyroidism in dialysis patients, paricalcitol treatment has comparable ≥50% reduction of parathyroid hormone (risk ratio [RR] = 1.33; 95% CI = 0.93-1.91;

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“…The yields for converting steroidal frameworks to secosteroids by photolysis and thermal isomerization are usually moderate or low, since several structural byproducts such as lumisterol, tachisterol, etc. are formed [14].…”

Section: Analogs For the Treatment Of Osteoporosismentioning

confidence: 99%

“…The 5,7-diene moiety in (12) was protected by adduct formation with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) to give PTAD adduct (13) in 80% yield from (11). The hydroxyl group in (13) was protected as its tert-butyldimethylsilyl (TBS) ether (14) in 95% yield, which was then regio-and stereoselectively epoxidized with m-chloroperbenzoic zcid (MCPBA) to give 1,2a-epoxide (15) in 78% yield. Retrocycloaddition of the PTAD adduct (15) to regenerate the 5,7-diene system in (16) in 75% yield was carried out by simply heating (140 C) (15) in 1,3-dimethyl-2-imidazolidinone (DMI).…”

Section: Analogs For the Treatment Of Osteoporosismentioning

confidence: 99%

Analogs for the Treatment of Osteoporosis ∗

Kubodera¹,

Takahashi²

2011

Vitamin D

Self Cite

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A New Look at the Most Successful Prodrugs for Active Vitamin D (D Hormone): Alfacalcidol and Doxercalciferol

Cited by 34 publications

References 36 publications

Long-term complications in patients with chronic hypoparathyroidism: a cross-sectional study

Long-term complications in patients with chronic hypoparathyroidism: a cross-sectional study

Comparison of Paricalcitol and Calcitriol in Dialysis Patients With Secondary Hyperparathyroidism: A Meta‐Analysis of Randomized Controlled Studies

Analogs for the Treatment of Osteoporosis ∗

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