Predictors of bone mineral density in patients receiving glucocorticoid replacement for Addison’s disease

• Published in: Endocrine 2024-05, Vol.84 (2), p.711-719
• Main Authors: Furman, Katarzyna, Gut, Paweł, Sowińska, Anna, Ruchała, Marek, Fichna, Marta
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Adaptor Proteins, Signal Transducing; Addison Disease - blood; Addison Disease - drug therapy; Adult; Aged; Alkaline phosphatase; Alkaline Phosphatase - blood; Biomarkers - blood; Body mass; Bone density; Bone Density - drug effects; Bone mineral density; Bone Remodeling - drug effects; Bone turnover; Collagen; Collagen Type I - blood; Dehydroepiandrosterone; Densitometry; Diabetes; Dkk1 protein; Dual energy X-ray absorptiometry; Endocrinology; Female; Genetic Markers; Glucocorticoids; Glucocorticoids - administration & dosage; Glucocorticoids - adverse effects; Hormone Replacement Therapy; Humanities and Social Sciences; Humans; Hydrocortisone; Hydrocortisone - blood; Intercellular Signaling Peptides and Proteins - blood; Internal Medicine; Lumbar Vertebrae - diagnostic imaging; Lumbar Vertebrae - drug effects; Male; Males; Medicine; Medicine & Public Health; Middle Aged; multidisciplinary; Original Article; Osteocalcin; Osteocalcin - blood; Osteopenia; Osteoporosis; Osteoporosis - blood; Peptide Fragments - blood; Peptides - blood; Post-menopause; Procollagen; Procollagen - blood; Science; SOST protein; Spine (lumbar); Young Adult
• ISSN: 1559-0100; 1355-008X; 1559-0100
• DOI: 10.1007/s12020-024-03709-3

Purpose Patients receiving long-term glucocorticoid (GC) treatment are at risk of osteoporosis, while bone effects of substitution doses in Addison’s disease (AD) remain equivocal. The project was aimed to evaluate serum bone turnover markers (BTMs): osteocalcin, type I procollagen N-terminal propeptide (PINP), collagen C-terminal telopeptide (CTX), sclerostin, DKK-1 protein, and alkaline phosphatase (ALP) in relation to bone mineral density (BMD) during GC replacement. Methods Serum BTMs and hormones were assessed in 80 patients with AD (22 males, 25 pre- and 33 postmenopausal females) on hydrocortisone (HC) substitution for ≥3 years. Densitometry with dual-energy X-ray absorptiometry covered the lumbar spine (LS) and femoral neck (FN). Results Among BTMs, only PINP levels were altered in AD. BMD Z-scores remained negative except for FN in males. Considering T-scores, osteopenia was found in LS in 45.5% males, 24% young and 42.4% postmenopausal females, while osteoporosis in 9.0%, 4.0% and 21.1%, respectively. Lumbar BMD correlated positively with body mass ( p  = 0.0001) and serum DHEA-S ( p  = 9.899 × 10 −6 ). Negative correlation was detected with HC dose/day/kg ( p  = 0.0320), cumulative HC dose ( p  = 0.0030), patient’s age ( p  = 1.038 × 10 −5 ), disease duration ( p  = 0.0004), ALP activity ( p  = 0.0041) and CTX level ( p  = 0.0105). However, only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of LS BMD. Conclusion Standard HC substitution does not considerably accelerate BMD loss in AD patients and their serum BTMs: CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remain within the reference ranges. Independent predictors of low lumbar spine BMD, especially ALP activity, serum CTX and sclerostin, might be monitored during GC substitution.