Bone mineral density and trabecular bone score in patients with 21‐hydroxylase deficiency after glucocorticoid treatment

Abstract

Objective Patients with 21‐hydroxylase deficiency (21‐OHD) are at risk of reduced bone mineral density (BMD) and fracture due to long‐term glucocorticoid treatment. Trabecular bone score (TBS) is complementary to conventional BMD as a marker for bone quality in patients with glucocorticoid‐induced osteoporosis. The purpose of this study is to evaluate the BMD and TBS in a cohort of patients with 21‐OHD and analyse factors related to TBS. Design An observational study. Patients A total of 46 21‐OHD adult patients treated with glucocorticoid for over 10 years who visited Peking Union Medical College Hospital between 2015 and 2019 were recruited. Eight male patients included in this study were all under 50 years old, and 38 female patients were all premenopausal. Measurements Diagnosis was confirmed by multiplex ligation‐dependent probe amplification combined with sequencing. Data were collected on physical characteristics, serum hormones and glucocorticoid treatment. Skeletal quality was evaluated by BMD and TBS, and factors related to TBS were analysed. Results Among the 46 patients, 2 (4.3%) had low BMD (Z‐score ≤ −2), while 11 (23.9%) patients had low TBS (degraded or partially degraded microarchitecture). The proportion of bone abnormality evaluated by TBS was higher than that by BMD (p < .001). Patients with lower TBS had significantly higher daily hydrocortisone dosage (p = .009 for males; p = .019 for females). TBS value was negatively correlated with daily hydrocortisone dosage (r = −.317, p = .026), and positively correlated with BMI in female patients (r = .345, p = .034). And there was a negative correlation between TBS value and the current age in male patients (r = −.741, p = .036). The distribution of genotypes (p = 1.000 for male; p = .567 for female) or phenotypes (p = .486 for male; p = .075 for female) had no statistical difference in patients with normal or abnormal TBS. Conclusions Approximately 24% of patients with 21‐OHD had abnormal microarchitecture of their bone in our study, and TBS score was negatively correlated with daily glucocorticoid dosage in patients. TBS may be used alongside conventional BMD as a complementary marker for bone evaluation in 21‐OHD patients.

Update on trabecular bone score

“…In general, compared to control subjects, TBS was reported to be lower in patients with diabetes (42,(57)(58)(59), primary hyperparathyroidism (60)(61)(62)(63)(64), acromegaly (65)(66)(67)(68), anorexia nervosa (69,70), hypercortisolism (71)(72)(73), primary aldosteronism (especially in women) (74), with prolonged GC exposure (75)(76)(77)(78)(79)(80)(81)(82)(83)(84), rheumatoid arthritis and rheumatic disease (85)(86)(87), aromatase inhibition (88), kidney transplant recipients (89), as well as in patients on hemodialysis (90,91). In differentiated thyroid carcinomas, TBS was found to be lower in patients receiving long-term suppressive doses of thyroid-stimulating hormone than in patients receiving shorter-term therapy (92)(93)(94).…”

Challenges in the diagnosis and management of glucocorticoid‐induced osteoporosis in younger and older adults

“…In YAs with CAH, including a cohort of premenopausal women aged 20–29 years 68 cumulative glucocorticoid dose is associated with low BMD 68–70 ; men with 21‐hydroxylase deficiency have lower spinal BMD than women 70,71 . Degraded TBS is associated with higher hydrocortisone doses and may be more prevalent than low BMD in CAH patients 72 . Total hip BMD is lower in patients with the salt‐wasting than the salt‐virilising subtype 69 …”

On quantification errors of R2*$$ {R}_2^{\ast } $$ and proton density fat fraction mapping in trabecularized bone marrow in the static dephasing regime

“…T * 2 and R * 2 measurements in trabecularized bone marrow have been correlated with the bone mineral density since early works [5][6][7][8][9] and R * 2 has been proposed as a biomarker for bone loss in osteoporosis. 1,[10][11][12] More recently the proton density fat fraction (PDFF) has been introduced as a biomarker of bone marrow fat content changes associated with bone loss. 1,2,[12][13][14] Therefore, chemical shift encoding-based (CSE) water-fat separation assuming a single R * 2 exponential signal decay has been proposed to simultaneously assess changes in the trabecular bone matrix by R * 2 quantification and in bone marrow fat content by PDFF quantification.…”

“…Beyond high‐resolution trabecular bone imaging, trabecular bone has been typically indirectly evaluated by measurements of effective bone marrow properties. $$$ {T}_2^{\ast } $$$ and $$$ {R}_2^{\ast } $$$ measurements in trabecularized bone marrow have been correlated with the bone mineral density since early works 5–9 and $$$ {R}_2^{\ast } $$$ has been proposed as a biomarker for bone loss in osteoporosis 1,10–12 . More recently the proton density fat fraction (PDFF) has been introduced as a biomarker of bone marrow fat content changes associated with bone loss 1,2,12–14 .…”