Endocrinol Metab.  2015 Mar;30(1):58-64. 10.3803/EnM.2015.30.1.58.

Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors

• Kim W
• Chung Y
• Kim SH
• Park S
• Bae JH
• Kim G
• Lee SJ
• Kim JE
• Park BW
• Lim SK
• Rhee Y

• KMID: 2407105
• DOI: http://doi.org/10.3803/EnM.2015.30.1.58

Abstract

BACKGROUND
Sclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs), which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass. We analyzed changes in serum sclerostin levels in Korean women with breast cancer who were treated with an AI.
METHODS
We included postmenopausal women with endocrine-responsive breast cancer (n=90; mean age, 57.7 years) treated with an AI, and compared them to healthy premenopausal women (n=36; mean age, 28.0 years). The subjects were randomly assigned to take either 5 mg alendronate with 0.5 microg calcitriol (n=46), or placebo (n=44) for 6 months.
RESULTS
Postmenopausal women with breast cancer had significantly higher sclerostin levels compared to those in premenopausal women (27.8+/-13.6 pmol/L vs. 23.1+/-4.8 pmol/L, P<0.05). Baseline sclerostin levels positively correlated with either lumbar spine or total hip bone mineral density only in postmenopausal women (r=0.218 and r=0.233; P<0.05, respectively). Serum sclerostin levels increased by 39.9%+/-10.2% 6 months after AI use in postmenopausal women; however, no difference was observed between the alendronate and placebo groups (39.9%+/-10.2% vs. 55.9%+/-9.13%, P>0.05).
CONCLUSION
Serum sclerostin levels increased with absolute deficiency of residual estrogens in postmenopausal women with endocrine-responsive breast cancer who underwent AI therapy with concurrent bone loss.

Keyword

Sclerostin; Breast neoplasms; Aromatase inhibitors; Osteoporosis

MeSH Terms

Alendronate
Aromatase Inhibitors*
Bone Density
Breast Neoplasms
Calcitriol
Estrogens*
Female
Hip
Humans
Osteocytes
Osteogenesis
Osteoporosis
Spine
Steroids
Alendronate
Aromatase Inhibitors
Calcitriol
Estrogens
Steroids

Figure

• 

  Fig. 1 Partial correlations between sclerostin, lumbar spine bone mineral density (BMD), and total hip BMD after adjusting for body mass index. (A, B) Premenopausal women. (C, D) Postmenopausal women. Circulating sclerostin positively correlated with lumbar spine and total hip BMD only in postmenopausal women (C, r=0.439, P<0.001; D, r=0.454, P<0.001, respectively). The age-adjusted correlation between BMD and sclerostin remained positive (data not shown). NS, not significant.

• 

  Fig. 2 Comparison of changes in sclerostin. Sclerostin was measured at baseline and after 24 weeks of aromatase inhibitor administration. We compared changes in sclerostin in the placebo and alendronate with calcitriol groups, and showed a significant increase in sclerostin levels in both groups (placebo group, P<0.05; alendronate with calcitriol group, P<0.05, by paired t test). However, the changes in sclerostin levels in the groups were not significantly different (P=not significant).

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