title: Insufficiency of PTH action on bone in uremia.
abstract: Abnormal bone turnover and mineral metabolism is observed in patients on dialysis. Secondary hyperparathyroidism (SHP) develops in response to mineral metabolism changes accompanying renal failure. As a factor of disease progression, the phenomenon of skeletal resistance to parathyroid hormone (PTH) is observed. With recent advances in the treatment of SHP, over-secretion of PTH can now be controlled. However, blood PTH levels 2 to 3 times higher than normal are considered necessary to maintain normal bone turnover in patients with renal failure. Various causes of skeletal resistance to PTH have been reported, including decrease in PTH receptor in osteoblasts, accumulation of 7-84 PTH fragment, and accumulation of osteoprotegerin. This skeletal resistance to PTH is not only a high-turnover bone accompanying SHP, but may also play a crucial role in the onset of low-turnover bone disease. We have produced a rat model of renal failure with normal level of PTH secretion and analyzed the bone of this model. Our results confirmed that bone turnover is lowered accompanying renal function impairment. We also found that this lowered bone turnover is improved by intermittent administration of PTH. In addition, PTH receptor gene expression is also decreased in low-turnover bone, as is observed in high-turnover bone disease. These findings confirm the presence of skeletal resistance to PTH in low-turnover bone accompanying renal failure. Control of calcium, phosphorus, and PTH levels with the target to maintain normal bone turnover is important in maintaining the quality of life of patients on dialysis.
authors.affiliation: Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, Japan. iwasaki@oita-nhs.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: H
authors.initials: H
authors.lastname: Yamato
authors.forename: T
authors.initials: T
authors.lastname: Nii-Kono
authors.forename: A
authors.initials: A
authors.lastname: Fujieda
authors.forename: M
authors.initials: M
authors.lastname: Uchida
authors.forename: A
authors.initials: A
authors.lastname: Hosokawa
authors.forename: M
authors.initials: M
authors.lastname: Motojima
authors.forename: M
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000097:blood / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood*; D051381:Rats; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications; D014511:Uremia / Q000097:blood* / Q000150:complications / Q000473:pathology
chemical_list: D010281:Parathyroid Hormone