Advances in the treatment of secondary and tertiary hyperparathyroidism

Li-xi, Zhang; Zhang, Ben; Liu, Xu-Yao; Wang, Ziming; Pan, Qi; Zhang, Tong-Yue; Zhang, Qiang

doi:10.3389/fendo.2022.1059828

Cited by 15 publications

(10 citation statements)

References 88 publications

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“…Secondary hyperparathyroidism is prone to cardiovascular hazards, such as cardiac and cerebrovascular accidents, vascular calcification and other problems 10 ; secondly, it can cause severe generalised itching of the skin, and if calcification occurs, the situation may be even more serious, and even skin ulcers and necrosis 11 ; and there is also the possibility that it may lead to bone damage, including bone pain, decreased bone density, fibrous osteitis, etc. pathological fractures and bone deformities, which will undoubtedly cause a greater impact on the patient's quality of life and working ability 12–14 . SHPT is complex and varied, seriously jeopardising patients' quality of life.…”

Section: Introductionmentioning

confidence: 99%

“…SHPT is complex and varied, seriously jeopardising patients' quality of life. However, there is no standardised treatment approach, especially in terms of surgical intervention and choice of clinical drug therapy 14,15 . As a result, it is critical to comprehend the effects of SHPT on the body and investigate various treatment possibilities.…”

Section: Introductionmentioning

confidence: 99%

“…pathological fractures and bone deformities, which will undoubtedly cause a greater impact on the patient's quality of life and working ability. 12 , 13 , 14 SHPT is complex and varied, seriously jeopardising patients' quality of life. However, there is no standardised treatment approach, especially in terms of surgical intervention and choice of clinical drug therapy.…”

Section: Introductionmentioning

confidence: 99%

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Capsiate ameliorates secondary hyperparathyroidism by improving insulin sensitivity and inhibiting angiogenesis

Li,

Zhou,

Wang

et al. 2024

J Cellular Molecular Medi

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Secondary hyperparathyroidism has a significant impact on the overall well‐being of the body. Capsiates, known for their antioxidant and metabolic properties, have emerged as a promising alternative treatment for secondary hyperparathyroidism. This study aims to evaluate the effects and mechanisms of capsiates in the treatment of secondary hyperparathyroidism. To achieve our research objectives, we conducted a study on patients' serum and examined changes in metabolic markers using serum metabolomics. We induced secondary hyperparathyroidism in rat through dietary intervention and divided them into four groups. The first group, referred to as the Parathyroid Hormone (PTH) group, received a low‐calcium and high‐phosphate diet (0.2% calcium, 1.2% phosphorus). The second group served as the control group, receiving a standard phosphate and calcium diet (0.6% calcium, 0.6% phosphorus). The third group, called the capsiates group, consisted of rat from the control group treated with capsiates (intraperitoneal injection of 2 mg/kg capsiates for 2 weeks after 2 weeks of dietary intervention). The fourth group was the capsiates‐treated PTH group. Subsequently, we conducted ribose nucleic acid (RNA) sequencing on parathyroid gland cells and evaluated serum thyroxine levels, oxidative stress, expression of proteins associated with vascular neogenesis, measurement of SOD, GSH and 3‐nitrotyrosine, micro‐CT and histological staining. The serum metabolomic data revealed a significant decrease in capsiate levels in the secondary hyperparathyroidism group. Administration of capsiates to PTH rat resulted in increased calcium levels compared to the PTH group. Additionally, the PTH + Capsiates group showed significantly lower levels of PTH and phosphate compared to the PTH group. The PTH group exhibited a notable increase in the quantity and size of mitochondria compared to the control group. Following capsiates administration to the PTH group, there was a significant reduction in the number of mitochondria and length of microvilli, but an increase in the size of mitochondria compared to the PTH group. Sequencing analysis revealed that vascular endothelial growth factor (VEGF) and Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) play crucial roles in this process. Vascular‐related variables and downstream signalling were significantly elevated in hyperthyroidism and were alleviated with capsaicin treatment. Finally, combining capsiates with the PTH group improved bone mineral density, Tb.N, BV.TV, Cs.Th, Tt.Ar, OPG, Ob.TV and Oc.TV, as well as the mineral apposition rate, but significantly decreased Tb.Sp and Receptor Activator for Nuclear Factor‐κ B Ligand (RANKL) compared to the PTH group. The findings suggest that capsiates can improve secondary hyperparathyroidism and ameliorated osteoporosis outcomes by inhibiting angiogenesis and reducing oxidative stress.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Capsiate ameliorates secondary hyperparathyroidism by improving insulin sensitivity and inhibiting angiogenesis

Li,

Zhou,

Wang

et al. 2024

J Cellular Molecular Medi

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“…Though it is effective, it may lead to hypercalcinemia in clininc. The mechanism of calcimimetic drugs is to activate the calcium-sensitive receptor (CaSR) on the main cells of the parathyroid gland [12] . The activated CaSR will suppress the release and synthesis of PTH, thus reducing the level of PTH in the blood.…”

Section: Introductionmentioning

confidence: 99%

The pharmacokinetics, pharmacodynamics and tolerability of SHR6508 in Chinese healthy subjects

ZHANG,

TAN,

YANG

et al. 2024

Preprint

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Background Secondary hyperparathyroidism (SHPT) mainly occurs in patients with chronic renal failure. SHR6508 is a new type of calcimimetic molecule, intended for patients with SHPT who are undergoing maintenance hemodialysis for chronic kidney disease. This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a new calcimimetic agent, SHR6508 injection, in healthy Chinese subjects. Methods In this phase I study, healthy subjects were administered SHR6508 injection via intravenous infusion according to a randomization table on the morning of the first day after admission. Blood samples were collected at 15 time points to measure the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of SHR6508. Adverse events that occurred during administration were also evaluated. Results 23 subjects were successfully screened and enrolled in the study. Except for 1 subject who withdrew from the study before medication, the remaining 22 subjects completed the study. No serious adverse events or adverse events leading to death occurred. The blood drug concentration of SHR6508 injection in healthy subjects reached its peak rapidly after a single intravenous dose. With the exception of the low-dose group, there was no significant difference in the distribution and elimination-related parameters Vz, t1/2z, and CLz between the other dose groups. The plasma drug exposure level (Cmax and AUC) of SHR6508 increased proportionally with the dose, and it showed linear pharmacokinetic characteristics within the dose range of 0.5-5 mg. The results of variance analysis showed no significant difference in PK characteristics between different genders. Conclusion After a single intravenous injection of 0.5-5 mg of SHR6508 injection in healthy subjects, the iPTH and blood calcium levels in the body decreased, and this effect showed dose-dependent characteristics, which is consistent with the expected effect of this product. The overall safety and tolerability of SHR6508 injection in healthy subjects after a single intravenous dose of 0.5-5 mg was good. Trial Registration: The trial is registered at chinadrugtrials.org.cn (ChiCTR2100048905)(19/07/2021).

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“…However, these guidelines have only applied the GRADE approach to systematic review evidence rather than the process of formulating final recommendations. As a result, clinical practices continue to lack standardization, especially regarding the selection of pharmacological therapies for PHPT 7 . Furthermore, surgery is one of the recommendations for most primary hyperparathyroidism and tertiary hyperparathyroidism patients, but the long-term effect is poor and a substantial subgroup exists who are asymptomatic and may not derive significant benefits from surgery 8 .…”

Section: Introductionmentioning

confidence: 99%

Unveiling potential drug targets for hyperparathyroidism through genetic insights via Mendelian randomization and colocalization analyses

Chen,

Wang,

et al. 2024

Sci Rep

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Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology. Cis-expression quantitative trait loci (cis-eQTL) data serving as genetic instrumental variables were obtained from the eQTLGen Consortium and Genotype-Tissue Expression (GTEx) portal. Hyperparathyroidism summary statistics for single nucleotide polymorphism (SNP) associations were sourced from the FinnGen study (5590 cases; 361,988 controls). Colocalization analysis was performed to determine the probability of shared causal variants underlying SNP-hyperparathyroidism and SNP-eQTL links. Five drug targets (CMKLR1, FSTL1, IGSF11, PIK3C3 and SLC40A1) showed significant causation with hyperparathyroidism in both eQTLGen and GTEx cohorts by MR analysis. Specifically, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and solute carrier family 40 member 1 (SLC40A1) showed strong evidence of colocalization with HPT. Multivariable MR and Phenome-Wide Association Study analyses indicated these two targets were not associated with other traits. Additionally, drug prediction analysis implies the potential of these two targets for future clinical applications. This study identifies PIK3C3 and SLC40A1 as potential genetically proxied druggable genes and promising therapeutic targets for hyperparathyroidism. Targeting PIK3C3 and SLC40A1 may offer effective novel pharmacotherapies for impeding hyperparathyroidism progression and reducing disease risk. These findings provide preliminary genetic insight into underlying drivers amenable to therapeutic manipulation, though further investigation is imperative to validate translational potential from preclinical models through clinical applications.

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Advances in the treatment of secondary and tertiary hyperparathyroidism

Cited by 15 publications

References 88 publications

Capsiate ameliorates secondary hyperparathyroidism by improving insulin sensitivity and inhibiting angiogenesis

Capsiate ameliorates secondary hyperparathyroidism by improving insulin sensitivity and inhibiting angiogenesis

The pharmacokinetics, pharmacodynamics and tolerability of SHR6508 in Chinese healthy subjects

Unveiling potential drug targets for hyperparathyroidism through genetic insights via Mendelian randomization and colocalization analyses

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