Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women.
BACKGROUND
Intermittent PTH treatment stimulates bone formation, but the mechanism(s) of this effect remain unclear. Sclerostin is an inhibitor of Wnt signaling, and animal studies have demonstrated that PTH suppresses sclerostin production.


OBJECTIVE
The objective of the study was to test whether intermittent PTH treatment of postmenopausal women alters circulating sclerostin levels.


METHODS
Prospective study.


METHODS
The study was conducted at a clinical research unit.


METHODS
Participants included 27 postmenopausal women treated with PTH (1-34) for 14 d and 28 control women.


METHODS
Serum sclerostin levels were measured.


RESULTS
Circulating sclerostin levels decreased significantly in the PTH-treated subjects, from (mean ± SEM) 551 ± 32 to 482 ± 31 pg/ml (-12.7%, P < 0.0001) but did not change in the control women (baseline, 559 ± 34 pg/ml; end point, 537 ± 40 pg/ml, P = 0.207; P = 0.017 for difference in changes between groups). Bone marrow plasma was obtained in a subset of the control and PTH-treated subjects (n = 19 each) at the end of the treatment period, and marrow plasma and peripheral serum sclerostin levels were significantly correlated (R = 0.64, P < 0.0001). Marrow plasma sclerostin levels were 24% lower in PTH-treated compared with control women, but perhaps due to the smaller sample size, this difference was not statistically significant (P = 0.173).


CONCLUSIONS
Circulating sclerostin levels correlate with bone marrow plasma levels and are reduced by intermittent PTH therapy in postmenopausal women. Further studies are needed to assess the extent to which decreases in sclerostin production contribute to the anabolic skeletal response to PTH.
Drake
Matthew T
MT
Division of Endocrinology and Metabolism, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Srinivasan
Bhuma
B
Mödder
Ulrike I
UI
Peterson
James M
JM
McCready
Louise K
LK
Riggs
B Lawrence
BL
Dwyer
Denise
D
Stolina
Marina
M
Kostenuik
Paul
P
Khosla
Sundeep
S
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000188:drug therapy; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D017698:Postmenopause / Q000097:blood*; D011446:Prospective Studies; D053245:RANK Ligand / Q000097:blood; D016896:Treatment Outcome
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; D053245:RANK Ligand; C422903:SOST protein, human; D015675:Osteocalcin