Preliminary report: Effect of adrenal androgen and estrogen on bone maturation and bone mineral density

Arisaka, Osamu; Hoshi, Megumi; Kanazawa, Sanae; Numata, Michio; Nakajima, Daisuke; Kanno, Shinko; Negishi, Masaho; Nishikura, Kiyoshi; Nitta, Akihisa; Imataka, M; Kuribayashi, Takeo; Kano, Kenichi

doi:10.1053/meta.2001.21678

Cited by 42 publications

(26 citation statements)

References 15 publications

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“…Multivariate linear regression did not underline another key period, maybe because of the lack of statistical power. Secondly, glucocorticoids may lead to osteoporosis (35), while androgens are known to increase bone formation markers (36,37). Many studies have pointed out that normal endogenous cortisol production is around 7 mg/m 2 per d in healthy people (38,39), whereas clinicians advocate 10-15 mg/m 2 per d of exogenous therapy (40), which can bring on corticosteroid side effects in bone and result in subnormal androgen levels.…”

Section: Discussionmentioning

confidence: 99%

“…Authors of published papers explained that estrogens have more protective action for bone mineralization than androgen (36,41), which could contribute to this result, all the more since the majority of women took exogenous estrogens. In addition, it appears that adult males with CAH face a dual problem: 1) adrenal steroid overproduction, especially androgen and progesterone that are less protective on BMD than testosterone, might interfere with follicle-stimulating hormone and luteinizing hormone production, resulting in gonadotropin deficiency and consequent small testicular size and lower testosterone levels (42,43), and 2) adrenal rests can interfere directly with the endocrine function of normal testicular tissue in a mechanical way or by local steroid production.…”

Section: Discussionmentioning

confidence: 99%

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Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency.

Chakhtoura

Bachelot²,

Samara-Boustani³

et al. 2008

European Journal of Endocrinology

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Objective: It remains controversial whether long-term glucocorticoids are charged of bone demineralization in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The aim of this study was to know whether cumulative glucocorticoid dose from the diagnosis in childhood to adulthood in patients with CAH had a negative impact on bone mineral density (BMD). Design: This was a retrospective study. Methods: Thirty-eight adult patients with classical and non-classical CAH were included. BMD was measured in the lumbar spine and femoral neck. Total cumulative glucocorticoid (TCG) and total average glucocorticoid (TAG) doses were calculated from pediatric and adult files. In the salt-wasting group, women were almost significantly endowed with a better BMD than men (PZ0.053). We found negative effects of TCG, TAG on lumbar (P!0.001, PZ0.002) and femoral T-scores (PZ0.006, P!0.001), predominantly during puberty. BMI was protective on BMD (PZ0.006). Conclusion: The TCG is an important factor especially during puberty for a bone demineralization in patients with 21-hydroxylase deficiency. The glucocorticoid treatment should be adapted particularly at this life period and preventive measures should be discussed in order to limit this effect.European Journal of Endocrinology 158 879-887

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency.

Chakhtoura

Bachelot²,

Samara-Boustani³

et al. 2008

European Journal of Endocrinology

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“…In patients with CAH, however, published data are conflicting. In previous studies of 21-OH deficiency, BMD has been shown to be unchanged (5)(6)(7)(8)(9), elevated (10,11), or decreased (12)(13)(14).…”

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confidence: 91%

“…The majority of subjects were young; five studies included prepubertal patients (5,7,8,10,11), whereas only two studies included subjects older than 35 yr of age (9,12).…”

mentioning

confidence: 99%

Long-Term Corticosteroid Replacement and Bone Mineral Density in Adult Women with Classical Congenital Adrenal Hyperplasia

King¹,

Wisniewski

Bankowski³

et al. 2006

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context: Concern has been raised regarding the potential impact of chronic glucocorticoid therapy on the bone mineral density (BMD) of patients with congenital adrenal hyperplasia (CAH).Objective: The purpose of this investigation was to assess the impact of chronic glucocorticoid replacement in adult women with classical CAH. Patients and Design:We used dual energy x-ray absorptiometry to evaluate lumbar spine and whole body BMD in 11 women with saltlosing (SL) CAH and 15 with the simple virilizing form. Physical characteristics and serum hormone concentrations were also measured. Results were compared with those of unaffected sisters of CAH patients (n ϭ 9).Main Outcome Measure: BMD was the main outcome measure. Results:Osteopenia was noted in 45% of SL CAH patients, 13% of patients with the simple virilizing form, and 11% of controls. Lumbar spine and whole body BMDs of CAH subjects were lower than those of controls (P Ͻ 0.05). Compared with CAH subjects with normal BMD, those with osteopenia had reduced serum levels of dehydroepiandrosterone sulfate and dehydroepiandrosterone. Adrenal androgen levels were particularly suppressed among postmenopausal women receiving glucocorticoid replacement. Conclusions

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“…Previous reports on bone mineral density (BMD) in CAH patients have been conflicting because some authors observed normal (7)(8)(9)(10)(11)(12)(13), some elevated (14,15), and some de-creased BMD (16 -20). The discrepancies may reflect differences in age of patients, type and severity of enzyme deficiencies, and various therapeutic regimes.…”

mentioning

confidence: 99%

Fractures and Bone Mineral Density in Adult Women with 21-Hydroxylase Deficiency

Falhammar

Filipsson

Holmdahl

et al. 2007

The Journal of Clinical Endocrinology &Amp; Metabolism

137

144

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Context:Patients with classical congenital adrenal hyperplasia (CAH) receive lifelong, often supraphysiological, glucocorticoid therapy. Pharmacological doses of glucocorticoids are an established risk factor for osteoporosis.Objective: Our objective was to evaluate bone mineral density (BMD), fracture prevalence, and markers of bone metabolism in adult females with CAH.Design: This was a cross-sectional observational study. Setting:Tertiary care referral centers were used in this study. Participants:We studied 61 women, aged 18 -63 yr, with genetically verified CAH due to 21-hydroxylase deficiency. They were patients with salt wasting (n ϭ 27), simple virilizing (n ϭ 28), and nonclassical 21-hydroxylase deficiency (n ϭ 6). A total of 61 age-matched women were controls. Main Outcome Measures:History of fractures was recorded. Total body, lumbar spine, and femoral neck BMD were measured by dualenergy x-ray absorptiometry. The World Health Organization criteria for osteopenia and osteoporosis were used. Serum marker of bone resorption, ␤-C telopeptide was studied. Results:The mean glucocorticoid dose in hydrocortisone equivalents was 16.9 Ϯ 0.9 mg/m 2 . Patients had lower BMD than controls at all measured sites (P Ͻ 0.001). In patients younger than 30 yr old, 48% were osteopenic vs. 12% in controls (P Ͻ 0.009). In patients 30 yr or older, 73% were osteopenic or osteoporotic vs. 21% in controls (P Ͻ 0.001). BMD was similar in the two classical forms and had no obvious relationship to genotypes. ␤-C-telopeptide was decreased in older patients. More fractures were reported in patients than controls (P Ͻ 0.001). The number of vertebrae and wrist fractures almost reached significance (P ϭ 0.058). Conclusions:Women with CAH have low BMD and increased fracture risk. BMD should be monitored, adequate prophylaxis and treatment instituted, and glucocorticoid doses optimized from puberty.

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Preliminary report: Effect of adrenal androgen and estrogen on bone maturation and bone mineral density

Cited by 42 publications

References 15 publications

Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency.

Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency.

Long-Term Corticosteroid Replacement and Bone Mineral Density in Adult Women with Classical Congenital Adrenal Hyperplasia

Fractures and Bone Mineral Density in Adult Women with 21-Hydroxylase Deficiency

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