Background Endocrine-related secondary osteoporosis (ERSOP) comprises disorders in which bone fragility results from hormonal abnormalities other than age-related or menopausal hypogonadism. Its prevalence is underestimated, and timely recognition is essential because many forms improve or reverse when the underlying endocrine disturbance is corrected.Objective This Review highlights the evolving concepts, unmet needs, and research opportunities in ERSOP, with focus on hypercortisolism, primary aldosteronism, male hypogonadism, hypercalciuria, and FGF23-dependent phosphate-wasting disorders.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels. Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels. Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels. Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels. Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels.Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Conclusion ERSOP should be considered in patients with atypical osteoporosis phenotypes, including men, younger adults, and individuals with normal BMD but fragility fractures. Optimal care requires structured endocrine assessment, correction of the primary disorder, and integration with bone-specific therapy where appropriate.
Endocrine-related osteoporosis: the state of the art
Gaudio, Agostino;
2026-01-01
Abstract
Background Endocrine-related secondary osteoporosis (ERSOP) comprises disorders in which bone fragility results from hormonal abnormalities other than age-related or menopausal hypogonadism. Its prevalence is underestimated, and timely recognition is essential because many forms improve or reverse when the underlying endocrine disturbance is corrected.Objective This Review highlights the evolving concepts, unmet needs, and research opportunities in ERSOP, with focus on hypercortisolism, primary aldosteronism, male hypogonadism, hypercalciuria, and FGF23-dependent phosphate-wasting disorders.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels. Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels. Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels. Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels. Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Recent findings Mild autonomous cortisol secretion (MACS) is increasingly recognized as a contributor to fracture risk even at near-normal cortisol levels.Primary aldosteronism promotes skeletal fragility via mineralocorticoid receptor activation, oxidative stress, hypercalciuria, and secondary hyperparathyroidism. Male hypogonadism is a major driver of bone loss, and optimal fracture prevention may require combined hormonal and anti-osteoporotic therapy. Differentiating PTH-dependent from PTH-independent hypercalciuria is crucial for management. FGF23-mediated phosphate-wasting disorders impair mineralization and may respond to targeted therapy, including burosumab.Conclusion ERSOP should be considered in patients with atypical osteoporosis phenotypes, including men, younger adults, and individuals with normal BMD but fragility fractures. Optimal care requires structured endocrine assessment, correction of the primary disorder, and integration with bone-specific therapy where appropriate.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
