Relationship Between Estrogen Treatment and Skeletal Health in Women With Cystic Fibrosis

Abstract BACKGROUND: Cystic fibrosis-related bone disease (CFBD) affects 26% of adults with cystic fibrosis (CF). CFBD increases the risk for fractures, which in turn limits patients’ ability to effectively perform daily therapies necessary to maintain health. Factors contributing to CFBD include nutritional deficiencies, inflammation, glucocorticoid use, CF-related diabetes and untreated hypogonadism. Hypogonadism in CF is thought to be functional, although the distribution of etiologies of female hypogonadism in the modern era of CF therapies is unknown. Estrogen supplementation is commonly prescribed in the form of oral contraceptives to women with low bone mineral density (BMD). At our CF center, the average dose of ethinyl estradiol prescribed to women is 20 mcg. Recent evidence suggests that oral estrogen is ineffective for restoring bone health in women with functional hypogonadism and specifically that doses < 30 mcg oral ethinyl estradiol are inadequate. It is unknown if estradiol supplementation will restore and/or maintain BMD in women with CFBD. METHODS: The purpose of this study was to examine the skeletal health of a cross-section of premenopausal women seen at a single CF center taking 20 mcg or less of ethinyl estradiol daily (low-dose estrogen) compared to women not taking estrogen supplement. As screening for an IRB-approved intervention study, we collected health information by chart review. RESULTS: In a 12-week period, 98 women were seen in CF clinic. Of women 18 - 50 years old with CF and a documented DXA, 37 women were not taking estrogen supplement (mean age 30.8 ± 5.9 years) and 6 women were taking low-dose estrogen (mean age 30.4 ± 7.1 years). There were not statistically significant differences in other baseline characteristics known to modify CFBD. Women not taking estrogen had higher lumbar spine z-score: -0.04 ± 1.0, compared to women taking low-dose estrogen, z-score: -0.7 ±, 0.5 (p-value 0.01). Women not taking estrogen had higher BMD at the lumbar spine: 1.02 ± 0.1 g/cm2, compared to women taking low-dose estrogen: 0.95 ± 0.1 g/cm2 (p-value 0.03). Similar trends were seen at the total hip and femoral neck (p-values > 0.05). DISCUSSION: In this retrospective single-center chart review, women not taking estrogen supplement compared to women taking low-dose estrogen supplement had higher BMD. This was statistically significant at the lumbar spine, the DXA site with mostly trabecular bone. Estrogen deficiency causes trabecular bone loss, which can be restored with estrogen supplementation. These findings raise concern that low-dose estrogen supplementation for women with CF is inadequate for optimal bone accrual and may be detrimental. The ideal route and dose of estrogen supplementation for skeletal health of premenopausal women with CF still needs to be clarified. REFERENCES: CFF Patient Registry 2017; Aris JCEM 2005; Ackerman JCEM 2019; Anabtawi J CF 2019; Hughan J CF 2019

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SUN-LB72 The Relationship Between Estrogen Exposure and Bone Health in Women With Cystic Fibrosis

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2075 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Neha Arora ◽

Malinda Wu ◽

Vin Tangpricha

Keyword(s):

Bone Mineral Density ◽

Cystic Fibrosis ◽

Bone Density ◽

Bone Mineral ◽

Bone Health ◽

Sex Hormone ◽

Estrogen Treatment ◽

Mineral Density ◽

Estrogen Exposure ◽

Exogenous Estrogen

Abstract Patients with cystic fibrosis (CF) are at risk for cystic fibrosis-related bone disease (CFBD) characterized by low bone mineral density and fractures. Nutritional status, cystic fibrosis-related diabetes (CFRD), lung health, and sex hormone insufficiency affect CFBD. CF Foundation guidelines recommend exogenous estrogen treatment for women with CFBD and sex hormone deficiency. There is a lack of data regarding effects of exogenous estrogen supplementation on the bone health of CF women. This Emory IRB approved case-control study examined the association of estrogen on bone health in CF women. Data included demographics, sex hormone treatments, CFBD modifiers, and bone mineral density. 35 estrogen exposed subjects were matched 1:2 to 70 estrogen unexposed subjects for age, BMI, and transplant status. Statistical tests analyzed differences in bone health outcomes between the estrogen and non-estrogen exposed groups. At baseline, age, BMI, transplant status, and CFRD were not statistically different (p>0.05) between the two groups. The unexposed group had higher rates of pancreatic insufficiency (p=0.02). The exposed and unexposed subjects did not have statistically significant differences in areal bone mineral density at lumbar spine, femoral neck, or total hip (p>0.05). Our study demonstrates that there are no differences in bone mineral density at 3 different sites between estrogen exposed versus estrogen unexposed women. One limitation is that factors that may also influence bone density including vitamin D status, family history, and severity of CF mutation were not corrected for. Future longitudinal studies should determine if estrogen treatment can increase bone density over time in CF women.

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Pregnancy in cystic fibrosis of the pancreas

JAMA ◽

10.1001/jama.195.12.993 ◽

1966 ◽

Vol 195 (12) ◽

pp. 993-1000 ◽

Cited By ~ 9

Author(s):

R. J. Grand

Keyword(s):

Cystic Fibrosis

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Freeze-Fracture Examination of Tight Junctions of Human Eccrine Sweat Glands

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002786 ◽

1980 ◽

Vol 38 ◽

pp. 634-635

Author(s):

J. V. Briggman ◽

J. Bigelow ◽

H. Bank ◽

S. S. Spicer

Keyword(s):

Cystic Fibrosis ◽

Freeze Fracture ◽

Sweat Glands ◽

Hypertonic Solution ◽

Dark Cells ◽

Clear Cells ◽

Junctional Complexes ◽

Secretory Coil ◽

Eccrine Sweat Glands ◽

Eccrine Sweat

The prevalence of strands shown by freeze-fracture in the zonula occludens of junctional complexes is thought to correspond closely with the transepi-thelial electrical resistance and with the tightness of the junction and its obstruction to paracellular flow.1 The complexity of the network of junc¬tional complex strands does not appear invariably related to the degree of tightness of the junction, however, as rabbit ileal junctions have a complex network of strands and are permeable to lanthanum. In human eccrine sweat glands the extent of paracellular relative to transcellular flow remains unknown, both for secretion of the isotonic precursor fluid by the coil and for resorption of a hypertonic solution by the duct. The studies reported here undertook, therefore, to determine with the freeze-fracture technique the complexity of the network of ridges in the junctional complexes between cells in the secretory coil and the sweat ducts. Glands from a patient with cystic fibrosis were also examined because an alteration in junctional strands could underlie the decreased Na+ resorption by sweat ducts in this disease. Freeze-fracture replicas were prepared by standard procedures on isolated coil and duct segments of human sweat glands. Junctional complexes between clear cells, between dark cells and between clear and dark cells on the main lumen, and between clear cells on intercellular canaliculi of the coil con¬tained abundant anastomosing closely spaced strands averaging 6.4 + 0.7 (mean + SE) and 9.0 +0.5 (Fig. 1) per complex, respectively. Thus, the junctions in the intercellular canaliculi of the coil appeared comparable in complexity to those of tight epithlia. Occasional junctions exhibited, in addition, 2 to 5 widely spaced anastomosing strands in a very close network basal to the compact network. The fewer junctional complexes observed thus far between the superficial duct cells consisted on the average of 6 strands arranged in a close network and 1 to 4 underlying strands that lay widely separated from one another (Fig. 2). The duct epitelium would, thus, be judged slightly more "leaky" than the coil. Infrequent junctional complexes observed to date in the secretory coil segment of a cystic fibrosis specimen disclosed rela¬tively few closely crowded strands.

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