1. Parathyroid hormone treatment for osteoporosis
Felicia Cosman Curr Opin Endocrinol Diabetes Obes . 2008 Dec;15(6):495-501. doi: 10.1097/MED.0b013e32831a46d6.
Purpose of review:There has recently been a dramatic expansion of clinical investigation of parathyroid hormone (PTH). There are no other anabolic agents on the horizon at the current time but clearly there are a large number of questions that remain about this powerful agent for osteoporosis.Recent findings:The present study reviews clinical trials using PTH alone and in combination and sequence with antiresorptive agents in postmenopausal women and briefly overviews trials in glucocorticoid-induced osteoporosis in men. PTH will be referred to as teriparatide when it is the recombinant human PTH(1-34) fragment produced by Lilly (Indianapolis, Indiana, USA) or the human PTH(1-34) produced by biochemical synthetic methods (Bachem, California, USA); and PTH(1-84) as the intact human recombinant molecule developed by NPS Pharmaceuticals (Salt Lake City, Utah, USA). PTH without other designation denotes either of the compounds.Summary:Because PTH improves microarchitecture, macroarchitecture and mass of bone, it might produce better long-term protection against fracture, when given first and followed by antiresorptive therapy, compared with antiresorptive agents alone. Results of studies on combination therapy must distinguish previously untreated vs. previously treated individuals. PTH should be considered in women with persistent osteoporosis on established bisphosphonates or raloxifene, in which adding PTH might produce better results than switching to PTH. There are still many unanswered questions concerning PTH therapy, one of the most important being the optimal regimen.
2. Parathyroid Hormone and Ischemic Cerebrovascular Event
Ali Coner,Hakan Altay,Cihan Altın,Haldun Muderrisoglu,Semih Giray Endocr Metab Immune Disord Drug Targets . 2019;19(8):1134-1140. doi: 10.2174/1871530319666190215150410.
Background:Increased parathyroid hormone (PTH) level is associated with coronary artery disease, hypertension and left ventricular hypertrophy which are all predisposing factors for the ischemic cerebrovascular event (ICVE). Carotid intima-media thickness (CIMT) and aortic distensibility are the two early, subclinical predictors of atherosclerosis. The relation of PTH with CIMT and aortic distensibility in patients with ICVE has not been previously studied.Objective:Our aim was to study the relationship of PTH levels with aortic distensibility and CIMT in patients with ICVE.Methods:Sixty-four ICVE patients and 50 control group were enrolled in the study. PTH levels, aortic distensibility and CIMT were measured in all individuals.Results:PTH levels were significantly higher in ICVE patients than in the controls (60.1±21.6 vs. 52.3±6.2 pg/ml) (p=0. 008). PTH levels were found to be inversely correlated with aortic distensibility (r= -0. 420, p=0.001) and positively correlated with CIMT (r:0, 285, p=0,002).Conclusion:The present study shows that PTH levels are increased in patients with acute ischemic cerebrovascular event compared to the control group. It also demonstrates that PTH levels are inversely related to aortic distensibility of ascending aorta and positively associated with CIMT.
3. Resveratrol inhibits parathyroid hormone-induced apoptosis in human aortic smooth muscle cells by upregulating sirtuin 1
Yingjie Liu,Zongli Diao,Yiru Wu,Weikang Guo,Wenhu Liu Ren Fail . 2019 Nov;41(1):401-407. doi: 10.1080/0886022X.2019.1605296.
Background:Cardiovascular disease is the leading cause of death in patients with chronic kidney disease, so there is an urgent need to identify therapeutic targets to control the progression of cardiovascular disease. Apoptosis of aortic smooth muscle cells can promote cardiovascular disease, but the role of parathyroid hormone (PTH) and sirtuin 1 in the pathophysiology of apoptosis is still unclear.Methods:Cultured human aortic smooth muscle cells (HASMCs) were stimulated with 10-6, 10-8, or 10-10mol/L PTH for different days, apoptosis was measured by flow cytometry and sirtuin 1 and Bcl-2 protein levels in cell extracts were analyzed by western blotting. HASMCs were stimulated with PTH (10-8mol/L) and 50 or 100 μmol/L RES for 3 d, apoptosis was measured by flow cytometry and sirtuin 1 and Bcl-2 protein levels in cell extracts were analyzed by western blotting.Results:We found that PTH decreased the expression of sirtuin 1 and Bcl-2, inducing apoptosis (p<.05). Resveratrol (RES), a sirtuin 1 agonist, inhibited PTH-induced apoptosis and restored Bcl-2 expression (p<.05).Conclusions:PTH induces apoptosis in HASMCs. Resveratrol inhibits PTH-induced apoptosis in HASMCs.
4. Use of recombinant human parathyroid hormone in hypocalcemic cardiomyopathy
Ghada El-Hajj Fuleihan,Edward M Brown,Ghada T Ballane,Jad G Sfeir,Habib A Dakik Eur J Endocrinol . 2012 Jun;166(6):1113-20. doi: 10.1530/EJE-11-1094.
Hypocalcemia secondary to hypoparathyroidism is a rare cause of congestive heart failure. However, its early recognition and treatment lead to significant improvement in cardiac function. We report a middle-aged woman presenting with symptoms of heart failure with a serum calcium level of 3.7 mg/dl and a serum inorganic phosphate level of 17.6 mg/dl 22 years after subtotal thyroidectomy. Besides calcium and calcitriol supplementation, she was the first patient with severe hypocalcemic cardiomyopathy to be given off-label recombinant human parathyroid hormone (PTH) because of an elevated serum calcium-phosphate product. We discuss the management and outcome of the patient and then present a brief review of similar previously reported cases. We also describe the pivotal role of calcium ion and the potential role of PTH in maintaining myocardial contractility, effective natriuresis, and possible pathogenic mechanisms contributing to heart failure secondary to hypocalcemia and hypoparathyroidism.
