Study of the Relationship Between Different Circulating Forms of Parathyroid Hormone and Histomorphometric Parameters of Bone Biopsy in Patients with CKD and Bone Mass Loss Before and After Bisphosphonate Treatment

• Grant number: 25/04872-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2025
• End date: March 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Aluízio Barbosa de Carvalho
• Grantee: Caio Prizon Silveira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 20/15744-9 - Osteoporosis in Chronic Kidney Disease, AP.TEM

Abstract

Mineral and bone disorders of chronic kidney disease (CKD-MBD) are one of the most common and early complications of CKD. CKD-MBD constitutes a syndrome that includes a set of biochemical changes (abnormalities in calcium and phosphorus metabolism, PTH, vitamin D, among others) and bone metabolism (alterations in bone remodeling, mineralization, and volume), along with the presence of vascular and/or soft tissue calcification. The alteration of parathyroid hormone (PTH) levels is the most important hormonal disturbance in CKD-MBD, and its measurement contributes to the diagnosis of renal osteodystrophy (ROD). Secondary hyperparathyroidism (SHPT), responsible for high-turnover bone disease, is characterized by high PTH levels, while adynamic bone disease (ABD), associated with low turnover, correlates with relatively lower levels of this hormone.The results obtained from PTH assays conducted since the 1960s to the present are controversial. Most of them fail to distinguish the intact, biologically active PTH molecule (1-84) from the carboxy-terminal fragments (mainly 7-84) or oxidized forms, both of which are considered inactive, thus complicating the interpretation of results. Intact PTH levels do not correlate with bone biopsy parameters, as previously demonstrated by others and our group. Therefore, the identification and quantification of different proteoforms of PTH are highly promising areas, especially in patients with CKD-MBD, and may contribute to a more accurate diagnosis and earlier intervention in ROD.Within the context of ROD, bone mass loss is a common finding, resulting from increased resorption and/or decreased bone formation. Recently, KDIGO recommended the use of bisphosphonates for the treatment of bone loss in patients with CKD. The main action of bisphosphonates in bone tissue is the reduction of bone resorption, leading to a gain in bone mass. Identifying the true concentration of biologically active PTH is essential in patients with CKD and bone mass loss undergoing bisphosphonate treatment.