Effects of androgen excess and glucocorticoid exposure on bone health in adult patients with 21-hydroxylase deficiency

https://doi.org/10.1016/j.jsbmb.2020.105734Get rights and content
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Highlights

  • Osteoporosis was rare in women with CAH but documented in 9.1% of men.

  • There was a significant positive correlation of Z scores at the spine with advancing age in women with CAH.

  • Intake of conventional hydrocortisone instead of synthetic glucocorticoids is associated with a higher bone mineral density in both sexes.

  • Higher sodium levels were associated with a lower BMD.

  • Neither in men nor in women, markers of androgen control were predictive for BMD at any site.

Abstract

Context: This study aimed to determine the role of modifiable predictors on bone health in congenital adrenal hyperplasia (CAH).

Design: Cross-sectional, single center study, including 97 patients (N = 42 men) with classic CAH due to 21-hydroxylase deficiency (N = 65 salt wasting, N = 32 simple virilizing).

Main Outcome Measures: Treatment-related predictors of bone health.

Results: Average T scores (-0.9 ± 1.4 vs. −0.4 ± 1.4; p = 0.036) as well as Z scores (-1.0 ± 1.3 vs. −0.1 ± 1.4; p = 0.012) at the spine in patients with CAH were significantly lower in men than women. While osteoporosis was rare in women, it was documented in 9.1% of men with CAH. There was a significant positive correlation of Z scores at the spine with advancing age in women with CAH (R² = 0.178; p = 0.003). In multivariate analysis, the intake of conventional hydrocortisone (HC) instead of synthetic glucocorticoids was independently associated with a higher bone mineral density (BMD) at the hip region in both sexes. In women, there was a positive association with vitamin D concentrations. Interestingly, higher sodium levels were associated with a lower BMD independent of renin levels and fludrocortisone dosage. Neither in men nor in women, markers of androgen control were predictive for BMD at any site. Markers of bone turnover indicated low bone turnover. No pathological fractures were documented.

Conclusions: Men with CAH are particularly prone to low bone density, while women seem to be relatively protected by androgen excess compared to the general female population. The use of HC instead of synthetic GCs for hormone replacement may translate into better bone health.

Abbreviations

17-OHP
17α-hydroxyprogesterone
ACTH
Adrenocorticotropic hormone
AVP
Arginin-Vasopressin
BAP
Bone alkaline phospatase
BMD
Bone mineral density
CAH
Congenital adrenal hyperplasia
CTX
C-terminal telopeptide of type 1 collagen
DXA
Dual energy X-ray absorptiometry
FC
Fludrocortisone
GC
Glucocorticoid(s)
HC
Hydrocortisone
OPG
Osteoprotegerin
PINP
procollagentype 1 N-terminal propeptide
PTH
Parathyroid hormone
RANKL
Receptor activator of NF-κB ligand
SHBG
Sex hormone-binding globulin
SV
Simple virilizing
SW
Salt-wasting

Keywords

Congenital adrenal hyperplasia
21-hydroxylase deficiency
BMD
Bone
Bone markers

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