Cortical bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Open accessAbstract
Summary: Background: Prior studies reveal that bone mineral density (BMD) in congenital adrenal hyperplasia (CAH) is mostly in the osteopaenic range and is associated with lifetime glucocorticoid dose. The forearm, a measure of cortical bone density, has not been evaluated. Objective: We aimed to evaluate BMD at various sites, including the forearm, and the factors associated with low BMD in CAH patients. Methods: Eighty CAH adults (47 classic, 33 nonclassic) underwent dual‐energy‐x‐ray absorptiometry and laboratory and clinical evaluation. BMD Z‐scores at the AP spine, total hip, femoral neck, forearm and whole body were examined in relation to phenotype, body mass index, current glucocorticoid dose, average 5‐year glucocorticoid dose, vitamin D, 17‐hydroxyprogesterone, androstenedione, testosterone, dehydroepiandrosterone and dehydroepiandrosterone sulphate (DHEAS). Results: Reduced BMD (T‐score <−1 at hip, spine, or forearm) was present in 52% and was more common in classic than nonclassic patients (P = 0·005), with the greatest difference observed at the forearm (P = 0·01). Patients with classic compared to nonclassic CAH, had higher 17‐hydroxyprogesterone (P = 0·005), lower DHEAS (P = 0·0002) and higher non‐traumatic fracture rate (P = 0·0005). In a multivariate analysis after adjusting for age, gender, height standard deviation, phenotype and cumulative glucocorticoid exposure, higher DHEAS was independently associated with higher BMD at the spine, radius and whole body. Conclusion: Classic CAH patients have lower BMD than nonclassic patients, with the most affected area being the forearm. This first study of forearm BMD in CAH patients suggests that low DHEAS may be associated with weak cortical bone independent of glucocorticoid exposure.
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- Findingown data
Classic CAH patients had a higher rate of non-traumatic fractures than nonclassic CAH patients.
“higher non-traumatic fracture rate (P = .0005)”
- Also stated in: § Results · plain
“The rate of non-traumatic fractures was significantly higher in classic as compared to nonclassic patients (36% vs. 3% respectively, P = .0005)”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
DHEAS was the only independent significant predictor of BMD at the forearm, whole body, and AP spine.
“DHEAS was the only independent significant predictor of BMD at the forearm, WB and AP spine.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Recent 5-year glucocorticoid exposure is representative of long-term glucocorticoid exposure.
- Findingown data
The BMD difference between classic and nonclassic CAH patients was largest at the forearm.
“with the greatest difference observed at the forearm (P = .01)”
- Also stated in: § Results · plain
“with the greatest difference observed at the forearm (Figure 1).”
Quote in the paperNot a substantial claim - Also stated in: § Results · plain
- Findingown data
After adjustment for age, sex, height SD, phenotype, and cumulative glucocorticoid exposure, higher DHEAS was independently associated with higher BMD at the spine, radius, and whole body.
“In a multivariate analysis after adjusting for age, sex, height standard deviation, phenotype, and cumulative glucocorticoid exposure, higher DHEAS was independently associated with higher BMD at the spine, radius, and whole body.”
- Also stated in: § Correlates of BMD · plain
“DHEAS showed a significant positive correlation with BMD at the spine, radius, and WB in the multivariate analysis.”
- Also stated in: § Discussion · plain
“Interestingly, we found that low DHEAS had an independent adverse effect on bone (spine, radius, and WB) after controlling for GC exposure in our final multivariate models.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Recent 5-year glucocorticoid exposure is representative of long-term glucocorticoid exposure.
- Also stated in: § Correlates of BMD · plain
- Findingown data
Classic CAH patients had lower BMD Z-scores than nonclassic patients at the AP spine, forearm, and whole body.
“Overall, patients with classic CAH tended to have lower BMD Z-scores than nonclassic patients at all sites; significant differences were observed at the AP spine (P = .015), forearm (P < .0001) and WB P = .048); with the greatest difference observed at the forearm (Figure 1).”
Quote in the paperSubstantial claim
- Findingown data
No correlation was found between glucocorticoid exposure and BMD.
“We did not find a correlation between GC exposure and BMD, similar to some prior studies 19, 20.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [19] Paganini C Radetti G Livieri C Braga V Migliavacca D Adami S 2000 Height, bone mineral density and bone markers in congenital adrenal hyperplasia Horm Res 54 164 168 11416232 source
Not checked in the free run.
- cites [20] Sciannamblo M Russo G Cuccato D Chiumello G Mora S 2006 Reduced bone mineral density and increased bone metabolism rate in young adult patients with 21-hydroxylase deficiency J Clin Endocrinol Metab 91 4453 4458 16926248 source
Not checked in the free run.
- The authors state this as an assumption: Recent 5-year glucocorticoid exposure is representative of long-term glucocorticoid exposure.
- Findingown data
Lower BMD at the radius was significantly associated with non-traumatic fractures.
“Lower BMD at the radius (but not other sites) was significantly associated with non-traumatic fractures (P = .008) (data not shown).”
Quote in the paperSubstantial claim - Findingown data
Women had higher BMD Z-scores than men at the spine and forearm.
“Women tended to have higher BMD Z-scores than men at all sites, however this was statistically different only at the spine (−0.01 ± 1.14 vs. −0.68 ± 0.9 respectively; P = .01) and forearm (0.24 ± 1.1 vs. −0.81 ± 2 respectively; P = .004).”
Quote in the paperNot a substantial claim - Findingown data
BMI was positively correlated with BMD only at the total hip and femoral neck.
“BMI was positively correlated with BMD only at the total hip and femoral neck (P < .05)”
Quote in the paperNot a substantial claim - Findingown data
Height SD was positively correlated with BMD at all measured sites.
“Height SD was positively correlated with BMD at all sites (P < .05)”
Quote in the paperNot a substantial claim - Findingown data
Classic CAH patients had lower DHEAS levels than nonclassic CAH patients.
“lower DHEAS (P = .0002)”
- Also stated in: § Results · plain
“significantly lower DHEA (P < .0001) and DHEAS (P = .0002) levels.”
Quote in the paperNot a substantial claim - Also stated in: § Results · plain
- Findingown data
In the adult CAH cohort, reduced BMD defined as a T-score below -1 at the hip, spine, or forearm was found in 52% of patients.
“Reduced BMD (T-score < −1 at hip, spine, or forearm) was present in 52%”
Quote in the paperSubstantial claim - Findingown data
Classic CAH patients had higher 17-hydroxyprogesterone levels than nonclassic CAH patients.
“Patients with classic compared to nonclassic CAH, had higher 17-hydroxyprogesterone (P = .005)”
- Also stated in: § Results · plain
“Classic patients compared to nonclassic patients had significantly higher 17-hydroxyprogesterone (P = .005)”
Quote in the paperNot a substantial claim - Also stated in: § Results · plain
- Findingown data
Age was positively related to BMD at the spine and radius after multivariate adjustment.
“age was positively related to BMD at the spine and radius even after adjusting for other variables in the multivariate analysis.”
Quote in the paperNot a substantial claim - Findingown data
Low BMD defined as a T-score below -1 was more common in classic than nonclassic patients at the AP spine, forearm, and whole body.
“Similarly, low BMD, defined as T-score < −1, was more common in classic than nonclassic patients at the AP spine, (36% vs. 9% respectively, P = .006); forearm (37% vs. 12% respectively, P = .01), and WB (32% vs. 9% respectively, P = .02).”
Quote in the paperSubstantial claim - Findingown data
Reduced BMD was more frequent in classic than in nonclassic CAH patients.
“was more common in classic than nonclassic patients (P = .005)”
- Also stated in: § Results · plain
“Low BMD at the spine, hip, or radius was more common in classic than nonclassic patients (65 vs. 33%; P = .005).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
CAH patients had the lowest BMD Z-scores at the forearm and spine.
“Similarly, we found that CAH patients had the lowest Z-scores at the forearm (wrist) and spine.”
Quote in the paperSubstantial claim - Premisecitation
Previous CAH studies report a prevalence of reduced BMD between 45% and 60%, compared with 52% in this cohort.
“Using the WHO definition of reduced BMD 16, the prevalence of reduced BMD in previous CAH studies ranges between 45–60% 3, 4, 17 as compared to 52% in our cohort.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [3] Bachelot A Plu-Bureau G Thibaud E Laborde K Pinto G Samara D Nihoul-Fekete C Kuttenn F Polak M Touraine P 2007 Long-term outcome of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency Horm Res 67 268 276 17170529 source
Not checked in the free run.
- cites [4] Falhammar H Filipsson H Holmdahl G Janson PO Nordenskjold A Hagenfeldt K Thoren M 2007 Fractures and bone mineral density in adult women with 21-hydroxylase deficiency J Clin Endocrinol Metab 92 4643 4649 17878254 source
Not checked in the free run.
- cites [17] Chakhtoura Z Bachelot A Samara-Boustani D Ruiz JC Donadille B Dulon J Christin-Maitre S Bouvattier C Raux-Demay MC Bouchard P Carel JC Leger J Kuttenn F Polak M Touraine P 2008 Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency Eur J Endocrinol 158 879 887 18390993 source
Not checked in the free run.
- Interpretationcitation
Low DHEAS levels in the classic CAH cohort were not solely due to glucocorticoid control but reflect the known blunted DHEA secretion of classic CAH.
“As such, low DHEAS levels in our cohort were not solely a reflection of GC control, but a well-known phenomenon of blunted DHEA secretion in patients with classic CAH.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [33] Volkl TM Ohl L Rauh M Schofl C Dorr HG 2011 Adrenarche and puberty in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Horm Res Paediatr 76 400 410 22123283 source
Not checked in the free run.
- cites [34] Helleday J Siwers B Ritzen EM Carlstrom K 1993 Subnormal androgen and elevated progesterone levels in women treated for congenital virilizing 21-hydroxylase deficiency J Clin Endocrinol Metab 76 933 936 8473408 source
Not checked in the free run.
- Premisecitation
Patients with classic CAH have low DHEAS levels in the first year of life, before and independently of treatment control.
“This is further supported by the fact that patients with classic CAH have low DHEAS levels in the first year of life, prior to and unrelated to treatment control, as evidenced by untreated patients with classic CAH who have low DHEAS levels despite high 17-OHP and T levels 33.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [33] Volkl TM Ohl L Rauh M Schofl C Dorr HG 2011 Adrenarche and puberty in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Horm Res Paediatr 76 400 410 22123283 source
Not checked in the free run.
- Interpretationreasoning
The association of low cortical bone with low DHEAS in classic CAH patients may be partly explained by disease-related DHEAS deficiency.
“Although this association does not imply causality, the finding of low cortical bone in association with low DHEAS in classic patients may be partially explained by disease-related DHEAS deficiency.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 12
- May combine two claims. 11
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThere was no correlation between height SD and DHEAS or DHEA.
“There was no correlation between height SD and DHEAS or DHEA.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataDHEA was associated with total hip and femoral neck BMD, but this association was no longer observed after adjustment for age, sex, height SD, and BMI.
“DHEA was associated with total hip and femoral neck BMD however this association was no longer observed after adjustment for age, sex, height SD, and BMI.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningBecause the study was not designed to evaluate BMD, data on exercise or family history of osteoporosis were not consistently available.
“As the study was not designed to evaluate BMD per se, data on exercise or family history of osteoporosis was not consistently available.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Study design and conductnone givenBMD measures may not necessarily reflect bone quality or fracture risk.
“Finally, BMD measures may not necessarily be reflective of bone quality, or risk of fractures.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataBone turnover markers were not available to further evaluate bone dynamics.
“We did not have bone turnover markers to further evaluate bone dynamics.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationDHEA acts on bone by binding to the androgen receptor and stimulating osteoblast growth and differentiation.
“DHEA exerts is effect on bone by binding to the androgen receptor (AR) and stimulating osteoblast growth and differentiation 23”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Kasperk CH Wakley GK Hierl T Ziegler R 1997 Gonadal and adrenal androgens are potent regulators of human bone cell metabolism in vitro J Bone Miner Res 12 464 471 9076590
Not checked in the free run.
May combine two claims.
PremisecitationDHEAS and other adrenal androgens influence bone homeostasis throughout life, especially during adrenarche, with a main effect on cortical bone.
“DHEAS and other adrenal androgens affect bone homeostasis throughout life and particularly during adrenarche, with a main effect on cortical bone.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [23] Kasperk CH Wakley GK Hierl T Ziegler R 1997 Gonadal and adrenal androgens are potent regulators of human bone cell metabolism in vitro J Bone Miner Res 12 464 471 9076590
Not checked in the free run.
- cites [24] Wang L Wang YD Wang WJ Zhu Y Li DJ 2007 Dehydroepiandrosterone improves murine osteoblast growth and bone tissue morphometry via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor J Mol Endocrinol 38 467 479 17446236
Not checked in the free run.
- cites [26] Remer T Boye KR Hartmann M Neu CM Schoenau E Manz F Wudy SA 2003 Adrenarche and bone modeling and remodeling at the proximal radius: weak androgens make stronger cortical bone in healthy children J Bone Miner Res 18 1539 1546 12929945
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe study was approved by the NICHD Institutional Review Board and all patients provided written informed consent.
“The study was approved by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Institutional Review Board and all patients provided written informed consent.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationChildren with classic CAH do not have the physiological rise in DHEAS during childhood, which accounts for the absence of typical adrenarche.
“Interestingly, children with classic CAH fail to have a physiological rise in DHEAS levels during childhood, effectively accounting for absence of a typical adrenarche 32, 33.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [32] Sellers EP MacGillivray MH 1995 Blunted adrenarche in patients with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency Endocr Res 21 537 544 7588424
Not checked in the free run.
- cites [33] Volkl TM Ohl L Rauh M Schofl C Dorr HG 2011 Adrenarche and puberty in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Horm Res Paediatr 76 400 410 22123283
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductnone givenDiagnoses were confirmed through biochemical and genetic testing.
“Diagnoses were confirmed through biochemical and genetic testing.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductreasoningThe study was not designed or advertised to evaluate BMD; BMD was part of the comprehensive clinical evaluation.
“The study was not designed or advertised to evaluate BMD. BMD was part of the comprehensive clinical evaluation performed.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA direct effect of DHEA on osteoblasts is suggested by a DHEA-specific receptor in mouse studies.
“a direct effect on osteoblasts has been suggested by a DHEA-specific receptor in mouse studies 24”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] Wang L Wang YD Wang WJ Zhu Y Li DJ 2007 Dehydroepiandrosterone improves murine osteoblast growth and bone tissue morphometry via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor J Mol Endocrinol 38 467 479 17446236
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductcitationPhenotypic classification was determined using clinical and hormonal criteria and had been previously reported.
“Phenotypic classification was determined based on clinical and hormonal criteria and has been previously reported 11.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Finkielstain GP Chen W Mehta SP Fujimura FK Hanna RM Van Ryzin C McDonnell NB Merke DP 2011 Comprehensive genetic analysis of 182 unrelated families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency J Clin Endocrinol Metab 96 E161 172 20926536 PMC3038490 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe study was cross-sectional, had limited historical data, and involved a heterogeneous sample.
“It is a cross-sectional study with limited historical data, and involves a heterogeneous sample.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe forearm is one of the most common sites for osteoporotic fractures in middle-aged and elderly women.
“the forearm is one of the most common sites for osteoporotic fractures in the middle aged and elderly women 36.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [36] Dhainaut A Hoff M Syversen U Haugeberg G 2013 Cortical hand bone porosity and its association with distal radius fracture in middle aged and elderly women PLoS One 8 e68405 23844197 PMC3700909
Not checked in the free run.
May combine two claims.
PremisecitationIn a study of 22 women with classic CAH, DHEAS was suppressed in a subset of 5 under-treated patients with elevated 17-OHP, supporting that low DHEAS in classic CAH is not solely a glucocorticoid treatment effect.
“In one study of 22 women with classic CAH, DHEAS levels were found to be suppressed in a subset of 5 under-treated patients with elevated 17-OHP 34, supporting the notion that low DHEAS found in classic CAH patients is not solely a GC treatment effect.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] Helleday J Siwers B Ritzen EM Carlstrom K 1993 Subnormal androgen and elevated progesterone levels in women treated for congenital virilizing 21-hydroxylase deficiency J Clin Endocrinol Metab 76 933 936 8473408
Not checked in the free run.
May combine two claims.
PremisecitationPatients with nonclassic CAH may have high DHEAS levels at diagnosis that decline with treatment but remain higher than in classic CAH and lower than in unaffected subjects.
“Patients with nonclassic CAH on the other hand may have high DHEAS levels upon diagnosis (as compared to controls) that subsequently decline upon treatment; however over time remain higher than patients with classic CAH but lower than unaffected subjects 35.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [35] Brunelli VL Chiumello G David M Forest MG 1995 Adrenarche does not occur in treated patients with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency Clin Endocrinol (Oxf) 42 461 466 7621563
Not checked in the free run.
May combine two claims.
PremisecitationOnly one study has found increased fracture risk in adult women with CAH compared with healthy controls, with fractures particularly involving the wrist and vertebrae.
“To date, only one study has found an increased fracture risk in adult women with CAH as compared to healthy controls, fractures particularly involved the wrist and vertebrae were found.4”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] Falhammar H Filipsson H Holmdahl G Janson PO Nordenskjold A Hagenfeldt K Thoren M 2007 Fractures and bone mineral density in adult women with 21-hydroxylase deficiency J Clin Endocrinol Metab 92 4643 4649 17878254
Not checked in the free run.
The authors state this as an assumption.
Recent 5-year glucocorticoid exposure is representative of long-term glucocorticoid exposure.
“Data on lifetime exposure to GC was not available, so assumptions were made based on recent 5-year exposure as representative of long-term GC exposure.”
The paper relies on this without support.
Forearm BMD had not been evaluated in CAH patients before this study.
“our study is the first to evaluate BMD of the forearm (distal radius), an assessment of cortical bone mass.”
“This first study of forearm BMD in CAH patients suggests that low DHEAS may be associated with weak cortical bone independent of glucocorticoid exposure.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Studies over the past two decades show evidence of lower BMD in patients with 21OH deficiency as compared to controls, with the prevalence of low BMD (osteoporosis or osteopenia) ranging from 37 to 81%, with some studies reporting increased fracture rate.
“Studies over the past two decades show evidence of lower BMD in patients with 21OH deficiency as compared to controls, with the prevalence of low BMD (osteoporosis or osteopenia) ranging from 37 to 81%, 94,[96][97][98] with some studies reporting increased fracture rate.96,99”
From Congenital adrenal hyperplasia (2017) · cites this paper as [96]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
DHEAS is not the sole independent BMD predictor
MajorThe summary calls DHEAS the only independent significant predictor at these sites, but the results also say age was positively related to spine and radius BMD after multivariate adjustment.
“DHEAS was the only independent significant predictor of BMD at the forearm, WB and AP spine.”
“Females had higher BMD than males, and age was positively related to BMD at the spine and radius even after adjusting for other variables in the multivariate analysis.”
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Hormonal determinants of bone turnover before and after attainment of peak bone mass
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Adrenomedullary Function in Patients with Nonclassic Congenital Adrenal Hyperplasia
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Congenital adrenal hyperplasia
El-Maouche, D., Arlt, W., & Merke, D. P. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31431-9 · Cited by 669 · see citing works
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Self-citationGlucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy
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Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia
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Falhammar, H., & Nordenström, A. (2015) · Endocrine · doi:10.1007/s12020-015-0656-0 · Cited by 127 · see citing works
Dissection of genetic variation and evidence for pleiotropy in male pattern baldness
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Falhammar, H., Frisén, L., Hirschberg, A. L., Nordenskjöld, A., Almqvist, C., & Nordenström, A. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab712 · Cited by 42 · see citing works
Jha, S., Turcu, A. F., Sinaii, N., Brookner, B., Auchus, R. J., & Merke, D. P. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa192 · Cited by 39 · see citing works
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Kocova, M., Anastasovska, V., & Falhammar, H. (2020) · Endocrine · doi:10.1007/s12020-020-02323-3 · Cited by 24 · see citing works
- Authors
- El‐Maouche, D., Collier, S., Prasad, M., Reynolds, J. C., & Merke, D. P.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Merke, Deborah P.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2014-06-28
- Volume
- 82
- Issue
- 3
- Pages
- 330-337
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- PMC
- PMC4242797
- OpenAlex
- W2088550987
- Semantic Scholar
- b10dd04853f4a941a1b19d0aea154d3ffb30ab00
- Cited by
- 53
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 5 · 2021: 4 · 2020: 9 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 5
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health Intramural Program
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- congenital adrenal hyperplasia, 21-hydroxylase deficiency, bone mineral density, cortical bone, forearm bone mineral density, glucocorticoid exposure, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, osteoporosis, fracture risk, vitamin D
- MeSH terms
- Adrenal Hyperplasia, Congenital, Adult, Female, Femur Neck, Forearm, Glucocorticoids, Humans, Male, Middle Aged, Pelvic Bones, Spine, Absorptiometry, Photon, Bone Density, Multivariate Analysis, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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