Responses of Urinary N-Telopeptide and Renal Calcium Handling to PTH Infusion after Treatment with Estrogen, Raloxifene, and Tamoxifen

Abstract

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.

Denosumab Improves Glomerular Filtration Rate in Osteoporotic Patients With Normal Kidney Function by Lowering Serum Phosphorus

“…Other studies have shown that administration of raloxifene, categorized as a SERM, significantly attenuated age‐related decrease in eGFR in postmenopausal women, while administration of raloxifene did not result in a significant decrease in serum Pi concentration . Furthermore, estrogen replacement therapy was reported to provide protection against increased serum PTH by attenuating the age‐related decline in eGFR following menopause .…”

“…Other studies have shown that administration of raloxifene, categorized as a SERM, significantly attenuated age-related decrease in eGFR in postmenopausal women, (3) while administration of raloxifene did not result in a significant decrease in serum Pi concentration. (36) Furthermore, estrogen replacement therapy was reported to provide protection against increased serum PTH by attenuating the age-related decline in eGFR following menopause. (36) Although another direct renoprotective mechanism by SERM or estrogen has been speculated, (5) our previous study showed that serum BAP, a reliable marker for bone turnover, (37) was significantly associated with urinary albumin excretion in postmenopausal but not premenopausal women, whereas serum Pi was significantly higher in that postmenopausal population.…”

“…(36) Furthermore, estrogen replacement therapy was reported to provide protection against increased serum PTH by attenuating the age-related decline in eGFR following menopause. (36) Although another direct renoprotective mechanism by SERM or estrogen has been speculated, (5) our previous study showed that serum BAP, a reliable marker for bone turnover, (37) was significantly associated with urinary albumin excretion in postmenopausal but not premenopausal women, whereas serum Pi was significantly higher in that postmenopausal population. (6) Because bone turnover is significantly higher in postmenopausal women, as reflected by higher serum BAP, increased serum Pi may be accounted for by an increase in Pi released from bone tissues.…”

Endobiogeny: A Global Approach to Systems Biology (Part 2 of 2)

“…Estrogens stimulate osteoblasts to fix calcium, which requires active, carboxylated osteocalcin, which results in a decrease in serum decarboxylated osteocalcin. [172][173][174] TSH levels vary inversely with serum osteocalcin levels. [175][176][177] Serum osteocalcin is directly correlated with tumor growth in both hormone independent and hormone-dependent tumors.…”