Responses of urinary N-telopeptide and renal calcium handling to PTH infusion after treatment with estrogen, raloxifene, and tamoxifen.
This prospective, randomized, placebo-controlled study investigated whether estrogen, tamoxifen, and raloxifene protect the skeleton from the acute catabolic effects of continuous PTH(1-34) infusion. It was infused over 24 h in 25 postmenopausal women both before and while on medication for 16-20 weeks (estrogen n = 7, raloxifene n = 5, tamoxifen n = 7, placebo n = 6). Blood and urine samples were collected at baseline and every 4 h during the PTH(1-34) infusion and analyzed for calcium homeostasis, bone remodeling, and specific cytokines. Data for the premedication PTH(1-34) infusions were pooled. During the premedication PTH(1-34) infusions, serum calcium and urine phosphorus increased, while serum phosphorus and urine calcium declined. Osteocalcin decreased (mean 18%), while urine NTX increased (mean 315%). Serum IL-6 increased 260%, but there were no other cytokine changes as a result of the PTH(1-34) infusion. On medication, the mean peak change in NTX with PTH(1-34) infusion was less (77, 59, and 31 nM/mM with raloxifene, tamoxifen, and estrogen, respectively). The reduction in urine calcium excretion was prolonged with each agent but only significantly with estrogen. There was no reduction in the IL-6 elevation induced by PTH(1-34) with any medication. The differential skeletal resorption response to PTH(1-34) infusion after the treatments may reflect different potencies of these agents or variability in interaction with the estrogen receptor. Renal calcium conservation and the blunted response of bone resorption to PTH(1-34) infusion may be mechanisms by which estrogen and estrogen agonist/antagonist agents preserve bone mass.
Clinical Research/Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY 10993, USA. kulakjc@gmail.com
Carolina A M
CA
Kulak
Merav
M
Baz-Hecht
Jeri
J
Nieves
Victor
V
Shen
Robert
R
Lindsay
Felicia
F
Cosman
D002118:Calcium / Q000378:metabolism*; D024042:Collagen Type I / Q000652:urine*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D010455:Peptides / Q000652:urine*; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*
D024042:Collagen Type I; D004967:Estrogens; D015850:Interleukin-6; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D002118:Calcium